LAURA adverse reactions

In locally advanced, unresectable stage III EGFRm NSCLC following CRT
The majority of adverse reactions in LAURA were Grade 1 or 21

ADVERSE REACTIONS IN ≥10%
OF PATIENTS RECEIVING TAGRISSO IN LAURA1*

  TAGRISSO
(n=143)		 Placebo
(n=73)
Adverse Reaction Any Grade
(%)		 Grade
3 or 4
(%)		 Any Grade
(%)		 Grade
3 or 4
(%)
Respiratory, Thoracic, and Mediastinal Disorders
ILD/pneumonitis† 56 3.5 38 0
Cough‡ 20 0 15 0
Skin Disorders
Rash§ 39 0.7 19 0
Nail toxicityII 23 0 1.4 0
Dry skin 17 0.7 5 0
Pruritus 13 0 7 0
Gastrointestinal Disorders
Diarrhea# 36 2.1 14 0
Stomatitis** 15 0 5 0
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain†† 20 0.7 26 0
Infection and Infestation Disorders
COVID-19‡‡ 20 0.7 10 0
Pneumonia§§ 15 3.5 10 5
Metabolism and Nutrition Disorders
Decreased appetite 15 0.7 5 0
  • Serious adverse reactions were reported in 38% of patients treated with TAGRISSO. The most common serious adverse reactions (≥1%) included ILD/pneumonitis (13%), pneumonia (6%), and gastroenteritis (1.4%). Fatal adverse reactions occurred in 1.4% of patients who received TAGRISSO due to pneumonia (0.7%) and ILD/pneumonitis (0.7%)
  • Clinically relevant adverse reactions in LAURA in <10% of patients receiving TAGRISSO were dyspnea (8%), urinary tract infection (8%), alopecia (1.4%), urticaria (1.4%), epistaxis (0.7%), keratitis (0.7%), and QTc interval prolongation (0.7%). QTc interval prolongation represents the incidence of patients who had a QTc prolongation >500 msec

*NCI CTCAE v5.0.

†Includes radiation pneumonitis, radiation lung fibrosis, pneumonitis, ILD, pulmonary fibrosis.

‡Includes cough, productive cough.

§Includes rash, maculopapular rash, pustular rash, pruritic rash, folliculitis, papule, dermatitis, acneiform dermatitis, atopic dermatitis, eczema, asteatotic eczema, acne, urticaria.

||Includes nail bed disorder, nail disorder, nail discoloration, nail infection, onychoclasis, paronychia.

Includes dry skin, skin fissures, senile xerosis, xeroderma.

#Includes diarrhea, enteritis.

**Includes stomatitis, aphthous ulceration, mouth ulceration.

††Includes musculoskeletal chest pain, myalgia, arthritis, arthralgia, back pain, bone pain, musculoskeletal pain, neck pain, pain in extremity, spinal osteoarthritis.

‡‡Includes COVID-19 and COVID-19 pneumonia.

§§Includes pneumonia, aspiration pneumonia, viral pneumonia, Pneumocystis jirovecii pneumonia, Haemophilus pneumonia, lower respiratory tract infection.

Laboratory abnormalities, discontinuation and dose interruption rates in LAURA1

The majority of laboratory abnormalities were Grade 1 or 21

LABORATORY ABNORMALITIES WORSENING
FROM BASELINE IN ≥20% OF PATIENTS IN LAURA

  TAGRISSO
(n=143)		 Placebo
(n=73)
Laboratory Abnormality*†
 All Grades
(%)		 Grade 3 or 4
(%)		 All Grades
(%)		 Grade 3 or 4
(%)
Hematology 
Lymphopenia
 70 3.5 40 1.4
Leukopenia 66 2.8 24 0
Thrombocytopenia
 51 1.4 8 1.4
Neutropenia 42 2.1 15 1.4
  • A clinically relevant laboratory abnormality in LAURA that occurred in <20% of patients receiving TAGRISSO was increased blood creatinine (19%)

Discontinuation and dose interruption rates due to ARs1

  • Permanent discontinuation: 13% of patients treated with TAGRISSO
    • The adverse reactions resulting in permanent discontinuation of TAGRISSO in >1 patient were ILD/pneumonitis (7%) and pneumonia (1.4%)
  • Dose interruptions: 56% of patients treated with TAGRISSO
    • The adverse reactions requiring dose interruption in ≥2% of patients were ILD/pneumonitis (35%), pneumonia (6%), COVID-19 (4.2%), neutropenia (2.1%), and QTc interval prolongation (2.1%)

Median duration of exposure and follow-up2

  • The median duration of exposure to TAGRISSO was 24.0 months
  • Median duration of investigator follow-up was 22.0 months in the TAGRISSO arm and 5.6 months in the placebo arm

*NCI CTCAE v5.0.

†Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available (TAGRISSO arm: 142 and placebo arm: 72).

In the LAURA study, adverse reaction of interest: ILD/pneumonitis1

  TAGRISSO
(n=143)		 Placebo
(n=73)
Adverse Reaction
 Any Grade
(%)		 Grade 3 or 4 (%) Any Grade
(%)		 Grade 3 or 4 (%)
ILD/pneumonitis* 56 3.5 38 0
  • Following definitive platinum-based CRT, ILD/pneumonitis, including radiation pneumonitis, occurred in 56% (80/143) of patients who received TAGRISSO monotherapy and 38% (28/73) of patients who received placebo
  • In the TAGRISSO arm, Grade 1 ILD/pneumonitis was observed in 18% of patients, Grade 2 in 34%, Grade 3 in 3.5%, and there was one fatal case (0.7%)
  • In the TAGRISSO arm (n=143), ILD/pneumonitis led to the following:
    • 35% (n=50) of patients had dosage interruptions
    • 32% (n=46) of patients were rechallenged with TAGRISSO. Of those, 11% (n=5) had recurrence of ILD/pneumonitis
    • 7% (n=10) of patients had permanent discontinuation
  • In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%

DOSAGE MODIFICATIONS FOR ILD/PNEUMONITIS FOR PATIENTS WHO HAVE RECEIVED DEFINITIVE PLATINUM-BASED CRT

Grade 1 ILD/pneumonitis Withhold or continue TAGRISSO, as clinically indicated
Grade ≥2 ILD/pneumonitis Permanently discontinue TAGRISSO

*Includes radiation pneumonitis, radiation lung fibrosis, pneumonitis, ILD, pulmonary fibrosis.

See dose modifications
for TAGRISSO
 

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  • There are no contraindications for TAGRISSO
  • TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy; 0.4% of cases were fatal

    • ILD/Pneumonitis with TAGRISSO in combination with Pemetrexed and Platinum-based Chemotherapy:

    • In the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 0.4% of cases were fatal

    • ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT):

    • In the LAURA study, following definitive platinum-based CRT, ILD/pneumonitis including radiation pneumonitis, occurred in 80 of the 143 patients (56%) who received TAGRISSO monotherapy and 28 of the 73 patients (38%) who received placebo. There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO-treated patients, ILD/pneumonitis led to permanent discontinuation of TAGRISSO in 7% of patients and dosage interruptions of TAGRISSO in 35% of patients. Among the 46 patients who were rechallenged with TAGRISSO, 11% had recurrence of ILD/pneumonitis. In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%

    • For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum-based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis

  • TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Clinical trials of TAGRISSO did not enroll patients with baseline QTc of >470 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
  • TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. In the LAURA study, following platinum-based CRT, 3% (4/135) of TAGRISSO-treated patients and no placebo-treated patients experienced LVEF decreases ≥10% and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
  • Keratitis was reported in 0.6% of 1813 patients treated with TAGRISSO monotherapy in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
  • Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed
  • Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
  • Aplastic anemia has been reported in TAGRISSO-treated patients in clinical trials (0.06% of 1813) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
  • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose
  • Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose
  • Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
    • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
    • TAGRISSO monotherapy following platinum-based chemoradiation therapy: lymphopenia, leukopenia, ILD/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough and COVID-19
    • TAGRISSO in combination with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine

INDICATIONS

  • TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the treatment of adult patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

Please see complete Prescribing Information, including Patient Information for TAGRISSO.

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1L, first-line; 2L, second-line; AUC, area under the curve; CI, confidence interval; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; CRT, chemoradiotherapy; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; po, by mouth; q3w, once every 3 weeks; qd, once daily; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. AstraZeneca Media Centre. AURA press release. https://www.astrazeneca.com/media-centre/press-releases/2015/TAGRISSO-AZD9291-approved-by-the-US-FDA-for-patients-with-EGFR-T790M-mutation-positive-metastatic-non-small-cell-lung-cancer-13112015.html. Published November 13, 2015. Accessed September 10, 2020. 3. FDA website. FDA approves osimertinib for first-line treatment of metastatic NSCLC with most common EGFR mutations. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-first-line-treatment-metastatic-nsclc-most-common-egfr-mutations. Published April 19, 2018. Accessed October 13, 2020. 4. FDA website. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations. Published December 18, 2020. Accessed August 11, 2021. 5. Tagrisso with the addition of chemotherapy approved in the US for patients with EGFR­-mutated advanced lung cancer [press release]. AstraZeneca Media Centre; February 16, 2024. 6. AstraZeneca Media Centre. LAURA press release. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-us-approval-in-unresectable-lung-cancer.html. Published September 26, 2024. Accessed September 26, 2024. 7. Data on File. US-89546. AstraZeneca Pharmaceuticals LP. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.10.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 23, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 9. AstraZeneca Media Centre. AURA3 press release. https://www.astrazeneca.com/media-centre/press-releases/2017/tagrisso-osimertinib-receives-us-fda-full-approval-31032017.html. Published March 31, 2017. Accessed September 10, 2020.
AEs, adverse events; AUC, area under the curve; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; PET, positron emission tomography; PK, pharmacokinetics; T790M, exon 20 threonine 790 methionine substitution; WT, wild-type. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 3. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046-1061. 4. Finlay MR, Anderton M, Ashton S, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014;57(20):8249-8267. 5. Ballard P, Yates JW, Yang Z, et al. Preclinical comparison of osimertinib with other EGFR-TKls in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130-5140. 6. Colclough N, Chen K, Johnström P, Fridén M, McGinnity DF. Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery. Drug Discov Today. 2019;24(5):1067-1073. 7. Varrone A, Varnäs K, Jucaite A, et al. A PET study in healthy subjects of brain exposure of 11C-labeled osimertinib—a drug intended for treatment of brain metastases in non-small cell lung cancer. J Cereb Blood Flow Metab. 2020;40(4):799-807.
Reference: 1. Data on File. US-74462. AstraZeneca Pharmaceuticals LP.

CI, confidence interval; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; TKI, tyrosine kinase inhibitor.

References: 1. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 3. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
AJCC, American Joint Committee on Cancer; CNS, central nervous system; ctDNA, circulating tumor DNA; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; OR, odds ratio; PD-L1, programmed death-ligand 1; RT, radiotherapy. References: 1. MacLean M, Luo X, Wang S, Kernstine K, Gerber DE, Xie Y. Outcomes of neoadjuvant and adjuvant chemotherapy in stage 2 and 3 non-small cell lung cancer: an analysis of the National Cancer Database. Oncotarget. 2018;9(36):24470-24479. 2. Lou F, Sima CS, Rusch VW, Jones DR, Huang J. Differences in patterns of recurrence in early-stage versus locally advanced non-small cell lung cancer. Ann Thorac Surg. 2014;98(5):1755-1760. 3. Galvez C, Jacob S, Finkelman BS, et al. The role of EGFR mutations in predicting recurrence in early and locally advanced lung adenocarcinoma following definitive therapy. Oncotarget. 2020;11(21):1953-1960. 4. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 5. Dong ZY, Zhang JT, Liu SY, et al. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. Oncoimmunology. 2017;6(11):e1356145. 6. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777 [supplementary appendix]. 7. D’Angelo SP, Janjigian YY, Ahye N, et al. Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib. J Thorac Oncol. 2012;7(12):1815-1822. 8. Cho JH, Zhou W, Choi YL, et al. Retrospective molecular epidemiology study of PD-L1 expression in patients with EGFR-mutant non-small cell lung cancer. Cancer Res Treat. 2018;50(1):95-102. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 10. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777. 11. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. 12. Cheema PK, Menjak IB, Winterton-Perks Z, et al. Impact of reflex EGFR/ALK testing on time to treatment of patients with advanced nonsquamous non-small-cell lung cancer. J Oncol Pract. 2017;13(2):e130-e138. 13. Anand K, Phung TL, Bernicker EH, Cagle PR, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442. 14. Freeman RK, Ascioti AJ, Dake M, Mahidhara RS. The effects of a multidisciplinary care conference on the quality and cost of care for lung cancer patients. Ann Thorac Surg. 2015;100(5):1834-1838.
AJCC, American Joint Committee on Cancer; CI, confidence interval; CNS, central nervous system; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; po, by mouth; PS, performance status; qd, once daily; QoL, quality of life; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186. 3. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. 4. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186 [protocol]. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147 [supplementary appendix]. 7. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [protocol]. 8. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643. 9. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643 [supplementary table]. 10. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. 11. Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):138-155. 12. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. 13. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [supplementary appendix]. 14. MacLean M, Luo X, Wang S, Kernstine K, Gerber DE, Xie Y. Outcomes of neoadjuvant and adjuvant chemotherapy in stage 2 and 3 non-small cell lung cancer: an analysis of the National Cancer Database. Oncotarget. 2018;9(36):24470-24479.
ARs, adverse reactions; CTCAE, Common Terminology Criteria for Adverse Events; NCI, National Cancer Institute; OS, overall survival; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. 3. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147.
AJCC, American Joint Committee on Cancer; ARs, adverse reactions; CI, confidence interval; CNS, central nervous system; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NE, not estimable; NSCLC, non-small cell lung cancer; OR, odds ratio; OS, overall survival; po, by mouth; qd, once daily; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia; RT, radiotherapy; TKI, tyrosine kinase inhibitor. References: 1. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 2014;3(4):242-249. 2. Chouaid C, Danson S, Andreas S, et al. Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS burden of illness study. Lung Cancer. 2018;124:310-316. 3. MacLean M, Luo X, Wang S, Kernstine K, Gerber DE, Xie Y. Outcomes of neoadjuvant and adjuvant chemotherapy in stage 2 and 3 non-small cell lung cancer: an analysis of the National Cancer Database. Oncotarget. 2018;9(36):24470-24479. 4. Lou F, Sima CS, Rusch VW, Jones DR, Huang J. Differences in patterns of recurrence in early-stage versus locally advanced non-small cell lung cancer. Ann Thorac Surg. 2014;98(5):1755-1760. 5. Dong ZY, Zhang JT, Liu SY, et al. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. Oncoimmunology. 2017;6(11):e1356145. 6. Galvez C, Jacob S, Finkelman BS, et al. The role of EGFR mutations in predicting recurrence in early and locally advanced lung adenocarcinoma following definitive therapy. Oncotarget. 2020;11(21):1953-1960. 7. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777 [supplementary appendix]. 8. D'Angelo SP, Janjigian YY, Ahye N, et al. Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib. J Thorac Oncol. 2012;7(12):1815-1822. 9. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 10. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777. 11. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. 12. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 13. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186. 14. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. 15. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186 [protocol]. 16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 17. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147 [supplementary appendix]. 18. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [protocol]. 19. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643. 20. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643 [supplementary table]. 21. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. 22. Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):138-155. 23. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. 24. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [supplementary appendix]. 25. Freeman RK, Ascioti AJ, Dake M, Mahidhara RS. The effects of a multidisciplinary care conference on the quality and cost of care for lung cancer patients. Ann Thorac Surg. 2015;100(5):1834-1838. 26. Bilfinger TV, Albano D, Perwaiz M, Keresztes R, Nemesure B. Survival outcomes among lung cancer patients treated using a multidisciplinary team approach. Clin Lung Cancer. 2018;19(4):346-351. 27. Wang J, Kuo YF, Freeman J, Goodwin JS. Increasing access to medical oncology consultation in older patients with stage II-IIIA non-small-cell lung cancer. Med Oncol. 2008;25(2):125-132. 28. Postmus PE, Kerr KM, Oudkerk M, et al; ESMO Guidelines Committee. 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1L, first-line; 2L, second-line; CRT, chemoradiation therapy; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); NG, nasogastric; NSCLC, non-small cell lung cancer; po, by mouth; q3w, once every 3 weeks; qd, once daily; T790M, exon 20 threonine 790 methionine substitution. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-55578. AstraZeneca Pharmaceuticals LP. 3. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
CI, confidence interval; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
1L, first-line; AJCC, American Joint Committee on Cancer; ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; EHR, electronic health records; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; G12C, glycine-to-cysteine substitution at codon 12; HER2, human epidermal growth factor receptor; ICI, immune checkpoint inhibitor; ILD, interstitial lung disease; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; ORR, overall response rate; PD-L1, programmed death-ligand 1; QNS, quantity not sufficient; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor. 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AEs, adverse events; AUC, area under the curve; BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; CR, complete response; ctDNA, circulating tumor DNA; DoR, duration of response; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; OR, odds ratio; ORR, overall response rate; OS, overall survival; PET, positron emission tomography; PFS, progression-free survival; PK, pharmacokinetics; po, by mouth; PR, partial response; PS, performance status; qd, once daily; RECIST, Response Evaluation Criteria in Solid Tumors; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Ramalingam SS, Vansteenkiste J, Planchard D, et al; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41-50. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 5. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125 [protocol]. 6. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 7. Rangachari D, Yamaguchi N, VanderLaan PA, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer. 2015;88(1):108-111. 8. Reungwetwattana T, Nakagawa K, Cho BC, et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018;36(33):3290-3297. 9. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125 [supplementary appendix]. 10. Ballard P, Yates JW, Yang Z, et al. Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130-5140. 11. Colclough N, Chen K, Johnström P, Fridén M, McGinnity DF. Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery. Drug Discov Today. 2019;24(5):1067-1073. 12. Varrone A, Varnäs K, Jucaite A, et al. A PET study in healthy subjects of brain exposure of 11C-labeled osimertinib—a drug intended for treatment of brain metastases in non-small cell lung cancer.
J Cereb Blood Flow Metab. 2020;40(4):799-807.
ALT, alanine aminotransferase; ARs, adverse reactions; AST, aspartate transaminase; CTCAE, Common Terminology Criteria for Adverse Events; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; ILD, interstitial lung disease; NCI, National Cancer Institute; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia; RTI, respiratory tract infection; TKI, tyrosine kinase inhibitor. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125.
AUC, area under the curve; BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; CTCAE, Common Terminology Criteria for Adverse Events; EGFR, epidermal growth factor receptor; FDA, US Food and Drug Administration; HR, hazard ratio; NA, not applicable; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; ORR, overall response rate; PFS, progression-free survival; po, by mouth; PS, performance status; qd, once daily; QTc, heart-rate corrected QT interval; QTcF, corrected QT interval by Fridericia; RECIST, Response Evaluation Criteria in Solid Tumors; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Mok TS, Wu YL, Ahn MJ, et al; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629-640. 3. cobas® EGFR Mutation Test v2 [package insert]. Indianapolis, IN: Roche Molecular Systems, Inc.; 2021. 4. Guardant360 CDx [package insert]. Redwood City, CA: Guardant Health, Inc.; 2023.
EGFR, epidermal growth factor receptor; IO, immunotherapy; mNSCLC, metastatic non-small cell lung cancer; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.
1L, first-line; 2L, second-line; APPs, Advanced Practice Providers; AUC, area under the curve; BCRP, breast cancer resistance protein; CRT, chemoradiotherapy; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; CYP, cytochrome P450; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; LVEF, left ventricular ejection fraction; mNSCLC, metastatic non-small cell lung cancer; NG, nasogastric; NSCLC, non-small cell lung cancer; P-GP, P-glycoprotein; q3w, once every 3 weeks; qd, once daily; QTc, heart rate-corrected QT interval; T790M, exon 20 threonine 790 methionine substitution.References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
AR, adverse reaction; AUC, area under the curve; CTCAE, Common Terminology Criteria for Adverse Events; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFRm, epidermal growth factor receptor mutation; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; po, by mouth; q3w, once every 3 weeks; qd, once daily; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia.References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Planchard D, Jänne PA, Cheng Y, et al. FLAURA2: safety and CNS outcomes of first-line osimertinib ± chemotherapy in EGFRm advanced NSCLC [oral presentation]. 2023 ESMO Congress; October 20-24, 2023; Madrid, Spain. 3. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [supplementary appendix]. 4. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. 5. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol].
1L, first-line; 2L, second-line; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; LVEF, left ventricular ejection fraction; mNSCLC, metastatic non-small cell lung cancer; NG, nasogastric; NSCLC, non-small cell lung cancer; po, by mouth; q3w, once every 3 weeks; qd, once daily; T790M, exon 20 threonine 790 methionine substitution. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-55578. AstraZeneca Pharmaceuticals LP. 3. Data on File. US-74462. AstraZeneca Pharmaceuticals LP.
AUC, area under the curve; BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; CR, complete response; ctDNA, circulating tumor DNA; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; DoR, duration of response; ECG, electrocardiogram; eCRF, electronic case-report form; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; Ex19del, exon 19 deletion; HR, hazard ratio; ILD, interstitial lung disease; L858R, exon 21 leucine 858 arginine substitution; mOS, median overall survival; mPFS, median progression-free survival; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; po, by mouth; PR, partial response; PS, performance status; q3w, once every 3 weeks; qd, once daily; RECIST, Response Evaluation Criteria in Solid Tumors; TKI, tyrosine kinase inhibitor; WHO, World Health Organization.References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. 3. Valdiviezo N, Okamoto I, Hughes BGM, et al. First-line osimertinib ± platinum-pemetrexed in EGFRm advanced NSCLC: FLAURA2 post-progression outcomes [oral presentation]. Presented at: 2024 European Lung Cancer Congress; March 20-23, 2024; Prague, Czech Republic. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Jänne PA, Planchard D, Cheng Y, et al. Osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2) [oral presentation]. Presented at: 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore. 6. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [supplementary appendix]. 7. Jänne PA, Planchard D, Kobayashi K, et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2024;42(7):808-820. 8. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol].
1L, first-line; 2L, second-line; CRT, chemoradiotherapy; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; mNSCLC, metastatic non-small cell lung cancer; NSCLC, non-small cell lung cancer; T790M, exon 20 threonine 790 methionine substitution. Reference: 1. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
AUC, area under the curve; CI, confidence interval; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; mPFS, median progression-free survival; NE, not estimable; NSCLC, non-small cell lung cancer; PFS, progression-free survival; po, by mouth; q3w, once every 3 weeks; qd, once daily. Reference: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
1L, first-line; AJCC, American Joint Committee on Cancer; ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; CI, confidence interval; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; EHR, electronic health records; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; Ex19del, exon 19 deletion; G12C, glycine-to-cysteine substitution at codon 12; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; ICI, immune checkpoint inhibitor; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; PD-L1, programmed death-ligand 1; PFS, progression-free survival; QNS, quantity not sufficient; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; SCLC, small cell lung cancer; SEER, Surveillance, Epidemiology, and End Results; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor. References: 1. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596-609. 2. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153. 3. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 12, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Robert NJ, Espirito JL, Chen L, et al. Biomarker testing and tissue journey among patients with metastatic non-small cell lung cancer receiving first-line therapy in The US Oncology Network. Lung Cancer. 2022;166:197-204. 6. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187 [supplementary appendix 2]. 7. Data on File. US-76421. AstraZeneca Pharmaceuticals LP. 8. Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321-1328. 9. Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321-1328 [supplemental table]. 10. Dietel M, Savelov N, Salanova R, et al. Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non–small-cell lung cancer: the global, multicenter EXPRESS study. Lung Cancer. 2019;134:174-179. 11. D’Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95-102. 12. Brown H, Vansteenkiste J, Nakagawa K, et al. Programmed cell death ligand 1 expression in untreated EGFR mutated advanced NSCLC and response to osimertinib versus comparator in FLAURA. J Thorac Oncol. 2020;15(1):138-143. 13. Lumakras [package insert]. Thousand Oaks, CA: Amgen Inc.; 2023. 14. Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021;384(25):2371-2381. 15. ENHERTU [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2022. 16. Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res. 2019;25(15):4691-4700. 17. Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173-180. 18. Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631-1641. 19. Peters S, Bexelius C, Munk V, Leighl N. The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer. Cancer Treat Rev. 2016;45:139-162. 20. Su PL, Wu YL, Chang WY, et al. Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer. Ther Adv Med Oncol. 2018;10:1758835918797589. 21. Koyama N, Watanabe Y, Iwai Y, et al. Distinct benefit of overall survival between patients with non-small-cell lung cancer harboring EGFR exon 19 deletion and exon 21 L858R substitution. Chemotherapy. 2017;62(3):151-158. 22. Sheng M, Wang F, Zhao Y, et al. Comparison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment: a meta-analysis. Eur J Clin Pharmacol. 2016;72(1):1-11. 23. Li J, Zhu H, Sun L, Xu W, Wang X. Prognostic value of site-specific metastases in lung cancer: a population based study. J Cancer. 2019;10(14):3079-3086. 24. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 25. Rangachari D, Yamaguchi N, VanderLaan PA, et al. Brain metastases in patients with EGFR-mutated or ALK rearranged non-small-cell lung cancers. Lung Cancer. 2015;88(1):108-111.
CI, confidence interval; CRT, chemoradiation therapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; mPFS, median progression-free survival; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; PFS, progression-free survival; PS, performance status. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; cCRT, concurrent chemoradiation therapy; CNS, central nervous system; CRT, chemoradiation therapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase.References: 1. Park SE, Noh JM, Kim YJ, et al. EGFR mutation is associated with short progression-free survival in patients with stage III non-squamous cell lung cancer treated with concurrent chemoradiotherapy. Cancer Res Treat. 2019;51(2):493-501. 2. Kim H, Park S, Jung HA, et al. EGFR mutation–positive unresectable stage III non-squamous lung cancer is associated with a high incidence of brain metastasis. Cancer Res Treat. 2023;55(2):498-505. 3. Tanaka K, Hida T, Oya Y, et al. EGFR mutation impact on definitive concurrent chemoradiation therapy for inoperable stage III adenocarcinoma. J Thorac Oncol. 2015;10(12):1720-1725. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 6. Aggarwal C, Bubendorf L, Cooper WA, et al. Molecular testing in stage I-III non-small cell lung cancer: approaches and challenges. Lung Cancer. 2021;162:42-53. 7. Anand K, Phung TL, Bernicker EH, Cagle PT, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442.
AJCC/UICC, American Joint Committee on Cancer/Union for International Cancer Control; ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; BRAF, v-raf murine sarcoma viral oncogene homolog B1; cCRT, concurrent chemoradiation therapy; CI, confidence interval; CNS, central nervous system; CR, complete response; CRT, chemoradiation therapy; CT, computed tomography; DoR, duration of response; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; Ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; ILD, interstitial lung disease; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; mPFS, median progression-free survival; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PR, partial response; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; sCRT, sequential chemoradiation therapy; SD, stable disease; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597. 3. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [supplementary appendix]. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Ramalingam SS, Özgüroğlu M, Ahn MJ, et al. Osimertinib after definitive chemoradiotherapy in patients with unresectable stage III EGFRm NSCLC: updated overall survival analysis from the LAURA study [oral presentation]. Presented at: European Lung Cancer Conference; March 26-29, 2025; Paris, France. 6. Lu S, Ahn MJ, Reungwetwattana T, et al. Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study. Ann Oncol. 2024;35(12):1116-1125. 7. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [protocol]. 8. Aggarwal C, Bubendorf L, Cooper WA, et al. Molecular testing in stage I-III non-small cell lung cancer: approaches and challenges. Lung Cancer. 2021;162:42-53. 9. Anand K, Phung TL, Bernicker EH, Cagle PR, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442. 10. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol].
ARs, adverse reactions; CRT, chemoradiation therapy; CTCAE, Common Terminology Criteria for Adverse Events; EGFRm, epidermal growth factor receptor mutation; ILD, interstitial lung disease; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; QTc, heart rate-corrected QT interval. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597.
ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; BRAF, v-raf murine sarcoma viral oncogene homolog B1; cCRT, concurrent chemoradiotherapy; CI, confidence interval; CNS, central nervous system; CR, complete response; CRT, chemoradiotherapy; CTCAE, Common Terminology Criteria for Adverse Events; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; Ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; ILD, interstitial lung disease; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MET, mesenchymal-epithelial transition; mOS, median overall survival; mPFS, median progression-free survival; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NCI, National Cancer Institute; NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PR, partial response; PS, performance status; QTc, heart rate-corrected QT interval; RECIST, Response Evaluation Criteria in Solid Tumors; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; SD, stable disease; TKI, tyrosine kinase inhibitor. References: 1. Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. 2. Bethune G, Bethune D, Ridgway N, Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010;2(1):48-51. 3. Kim H, Park S, Jung HA, et al. EGFR mutation–positive unresectable stage III non-squamous lung cancer is associated with a high incidence of brain metastasis. Cancer Res Treat. 2023;55(2):498-505. 4. Tanaka K, Hida T, Oya Y, et al. EGFR mutation impact on definitive concurrent chemoradiation therapy for inoperable stage III adenocarcinoma. J Thorac Oncol. 2015;10(12):1720-1725. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 7. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol]. 8. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597. 9. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [supplementary appendix]. 10. Ramalingam SS, Özgüroğlu M, Ahn MJ, et al. Osimertinib after definitive chemoradiotherapy in patients with unresectable stage III EGFRm NSCLC: updated overall survival analysis from the LAURA study [oral presentation]. Presented at: European Lung Cancer Conference; March 26- 29, 2025; Paris, France. 11. Lu S, Ahn MJ, Reungwetwattana T, et al. Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study. Ann Oncol. 2024;35(12):1116-1125. 12. Aggarwal C, Bubendorf L, Cooper WA, et al. Molecular testing in stage I-III non-small cell lung cancer: approaches and challenges. Lung Cancer. 2021;162:42-53. 13. Anand K, Phung TL, Bernicker EH, Cagle PR, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442. 14. Wald P, Mo X, Barney C, et al. Prognostic value of primary tumor volume changes on kV-CBCT during definitive chemoradiotherapy for stage III non–small cell lung cancer. J Thorac Oncol. 2017;12(12):1779-1787. 15. Jabbour SK, Kim S, Haider SA, et al. Reduction in tumor volume by cone beam computed tomography predicts overall survival in non-small cell lung cancer treated with chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2015;92(3):627-633.
1L, first-line; 2L, second-line; CTCAE, Common Terminology Criteria for Adverse Events; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; NCI, National Cancer Institute; NG, nasogastric; NSCLC, non-small cell lung cancer; QTc, heart rate-corrected QT interval; T790M, exon 20 threonine 790 methionine substitution. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; NSCLC, non-small cell lung cancer; PET, positron emission tomography; T790M, exon 20 threonine 790 methionine substitution; WT, wild-type. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 3. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046-1061. 4. Finlay MR, Anderton M, Ashton S, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014;57(20):8249-8267.
  • There are no contraindications for TAGRISSO
  • TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy; 0.4% of cases were fatal

    • ILD/Pneumonitis with TAGRISSO in combination with Pemetrexed and Platinum-based Chemotherapy:

    • In the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 0.4% of cases were fatal

    • ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT):

    • In the LAURA study, following definitive platinum-based CRT, ILD/pneumonitis including radiation pneumonitis, occurred in 80 of the 143 patients (56%) who received TAGRISSO monotherapy and 28 of the 73 patients (38%) who received placebo. There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO-treated patients, ILD/pneumonitis led to permanent discontinuation of TAGRISSO in 7% of patients and dosage interruptions of TAGRISSO in 35% of patients. Among the 46 patients who were rechallenged with TAGRISSO, 11% had recurrence of ILD/pneumonitis. In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%

    • For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum-based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis

  • TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Clinical trials of TAGRISSO did not enroll patients with baseline QTc of >470 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
  • TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. In the LAURA study, following platinum-based CRT, 3% (4/135) of TAGRISSO-treated patients and no placebo-treated patients experienced LVEF decreases ≥10% and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
  • Keratitis was reported in 0.6% of 1813 patients treated with TAGRISSO monotherapy in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
  • Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed
  • Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
  • Aplastic anemia has been reported in TAGRISSO-treated patients in clinical trials (0.06% of 1813) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
  • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose
  • Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose
  • Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
    • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
    • TAGRISSO monotherapy following platinum-based chemoradiation therapy: lymphopenia, leukopenia, ILD/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough and COVID-19
    • TAGRISSO in combination with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine

INDICATIONS

  • TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the treatment of adult patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

Please see complete Prescribing Information, including Patient Information for TAGRISSO.

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1L, first-line; 2L, second-line; AUC, area under the curve; CI, confidence interval; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; CRT, chemoradiotherapy; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; po, by mouth; q3w, once every 3 weeks; qd, once daily; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. AstraZeneca Media Centre. AURA press release. https://www.astrazeneca.com/media-centre/press-releases/2015/TAGRISSO-AZD9291-approved-by-the-US-FDA-for-patients-with-EGFR-T790M-mutation-positive-metastatic-non-small-cell-lung-cancer-13112015.html. Published November 13, 2015. Accessed September 10, 2020. 3. FDA website. FDA approves osimertinib for first-line treatment of metastatic NSCLC with most common EGFR mutations. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-first-line-treatment-metastatic-nsclc-most-common-egfr-mutations. Published April 19, 2018. Accessed October 13, 2020. 4. FDA website. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations. Published December 18, 2020. Accessed August 11, 2021. 5. Tagrisso with the addition of chemotherapy approved in the US for patients with EGFR­-mutated advanced lung cancer [press release]. AstraZeneca Media Centre; February 16, 2024. 6. AstraZeneca Media Centre. LAURA press release. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-us-approval-in-unresectable-lung-cancer.html. Published September 26, 2024. Accessed September 26, 2024. 7. Data on File. US-89546. AstraZeneca Pharmaceuticals LP. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.10.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 23, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 9. AstraZeneca Media Centre. AURA3 press release. https://www.astrazeneca.com/media-centre/press-releases/2017/tagrisso-osimertinib-receives-us-fda-full-approval-31032017.html. Published March 31, 2017. Accessed September 10, 2020.
AEs, adverse events; AUC, area under the curve; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; PET, positron emission tomography; PK, pharmacokinetics; T790M, exon 20 threonine 790 methionine substitution; WT, wild-type. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 3. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046-1061. 4. Finlay MR, Anderton M, Ashton S, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014;57(20):8249-8267. 5. Ballard P, Yates JW, Yang Z, et al. Preclinical comparison of osimertinib with other EGFR-TKls in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130-5140. 6. Colclough N, Chen K, Johnström P, Fridén M, McGinnity DF. Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery. Drug Discov Today. 2019;24(5):1067-1073. 7. Varrone A, Varnäs K, Jucaite A, et al. A PET study in healthy subjects of brain exposure of 11C-labeled osimertinib—a drug intended for treatment of brain metastases in non-small cell lung cancer. J Cereb Blood Flow Metab. 2020;40(4):799-807.
Reference: 1. Data on File. US-74462. AstraZeneca Pharmaceuticals LP.

CI, confidence interval; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; TKI, tyrosine kinase inhibitor.

References: 1. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 3. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
AJCC, American Joint Committee on Cancer; CNS, central nervous system; ctDNA, circulating tumor DNA; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; OR, odds ratio; PD-L1, programmed death-ligand 1; RT, radiotherapy. References: 1. MacLean M, Luo X, Wang S, Kernstine K, Gerber DE, Xie Y. Outcomes of neoadjuvant and adjuvant chemotherapy in stage 2 and 3 non-small cell lung cancer: an analysis of the National Cancer Database. Oncotarget. 2018;9(36):24470-24479. 2. Lou F, Sima CS, Rusch VW, Jones DR, Huang J. Differences in patterns of recurrence in early-stage versus locally advanced non-small cell lung cancer. Ann Thorac Surg. 2014;98(5):1755-1760. 3. Galvez C, Jacob S, Finkelman BS, et al. The role of EGFR mutations in predicting recurrence in early and locally advanced lung adenocarcinoma following definitive therapy. Oncotarget. 2020;11(21):1953-1960. 4. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 5. Dong ZY, Zhang JT, Liu SY, et al. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. Oncoimmunology. 2017;6(11):e1356145. 6. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777 [supplementary appendix]. 7. D’Angelo SP, Janjigian YY, Ahye N, et al. Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib. J Thorac Oncol. 2012;7(12):1815-1822. 8. Cho JH, Zhou W, Choi YL, et al. Retrospective molecular epidemiology study of PD-L1 expression in patients with EGFR-mutant non-small cell lung cancer. Cancer Res Treat. 2018;50(1):95-102. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 10. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777. 11. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. 12. Cheema PK, Menjak IB, Winterton-Perks Z, et al. Impact of reflex EGFR/ALK testing on time to treatment of patients with advanced nonsquamous non-small-cell lung cancer. J Oncol Pract. 2017;13(2):e130-e138. 13. Anand K, Phung TL, Bernicker EH, Cagle PR, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442. 14. Freeman RK, Ascioti AJ, Dake M, Mahidhara RS. The effects of a multidisciplinary care conference on the quality and cost of care for lung cancer patients. Ann Thorac Surg. 2015;100(5):1834-1838.
AJCC, American Joint Committee on Cancer; CI, confidence interval; CNS, central nervous system; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; po, by mouth; PS, performance status; qd, once daily; QoL, quality of life; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186. 3. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. 4. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186 [protocol]. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147 [supplementary appendix]. 7. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [protocol]. 8. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643. 9. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643 [supplementary table]. 10. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. 11. Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):138-155. 12. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. 13. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [supplementary appendix]. 14. MacLean M, Luo X, Wang S, Kernstine K, Gerber DE, Xie Y. Outcomes of neoadjuvant and adjuvant chemotherapy in stage 2 and 3 non-small cell lung cancer: an analysis of the National Cancer Database. Oncotarget. 2018;9(36):24470-24479.
ARs, adverse reactions; CTCAE, Common Terminology Criteria for Adverse Events; NCI, National Cancer Institute; OS, overall survival; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. 3. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147.
AJCC, American Joint Committee on Cancer; ARs, adverse reactions; CI, confidence interval; CNS, central nervous system; DFS, disease-free survival; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NE, not estimable; NSCLC, non-small cell lung cancer; OR, odds ratio; OS, overall survival; po, by mouth; qd, once daily; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia; RT, radiotherapy; TKI, tyrosine kinase inhibitor. References: 1. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 2014;3(4):242-249. 2. Chouaid C, Danson S, Andreas S, et al. Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS burden of illness study. Lung Cancer. 2018;124:310-316. 3. MacLean M, Luo X, Wang S, Kernstine K, Gerber DE, Xie Y. Outcomes of neoadjuvant and adjuvant chemotherapy in stage 2 and 3 non-small cell lung cancer: an analysis of the National Cancer Database. Oncotarget. 2018;9(36):24470-24479. 4. Lou F, Sima CS, Rusch VW, Jones DR, Huang J. Differences in patterns of recurrence in early-stage versus locally advanced non-small cell lung cancer. Ann Thorac Surg. 2014;98(5):1755-1760. 5. Dong ZY, Zhang JT, Liu SY, et al. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. Oncoimmunology. 2017;6(11):e1356145. 6. Galvez C, Jacob S, Finkelman BS, et al. The role of EGFR mutations in predicting recurrence in early and locally advanced lung adenocarcinoma following definitive therapy. Oncotarget. 2020;11(21):1953-1960. 7. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777 [supplementary appendix]. 8. D'Angelo SP, Janjigian YY, Ahye N, et al. Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib. J Thorac Oncol. 2012;7(12):1815-1822. 9. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 10. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777. 11. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. 12. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 13. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186. 14. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147. 15. Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non–small-cell lung cancer: updated results from the phase III randomized ADAURA trial [published online ahead of print January 31, 2023]. J Clin Oncol. doi:10.1200/JCO.22.02186 [protocol]. 16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 17. Tsuboi M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389(2):137-147 [supplementary appendix]. 18. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [protocol]. 19. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643. 20. Koch AL, Vellanki PJ, Drezner N, et al. FDA approval summary: osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review. Clin Cancer Res. 2021;27(24):6638-6643 [supplementary table]. 21. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. 22. Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer—major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):138-155. 23. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. 24. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723 [supplementary appendix]. 25. Freeman RK, Ascioti AJ, Dake M, Mahidhara RS. The effects of a multidisciplinary care conference on the quality and cost of care for lung cancer patients. Ann Thorac Surg. 2015;100(5):1834-1838. 26. Bilfinger TV, Albano D, Perwaiz M, Keresztes R, Nemesure B. Survival outcomes among lung cancer patients treated using a multidisciplinary team approach. Clin Lung Cancer. 2018;19(4):346-351. 27. Wang J, Kuo YF, Freeman J, Goodwin JS. Increasing access to medical oncology consultation in older patients with stage II-IIIA non-small-cell lung cancer. Med Oncol. 2008;25(2):125-132. 28. Postmus PE, Kerr KM, Oudkerk M, et al; ESMO Guidelines Committee. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl4):iv1-iv21. 29. Zuccato JA, Ellis PM. Improving referral of patients for consideration of adjuvant chemotherapy after surgical resection of lung cancer. Curr Oncol. 2012;19(6):e422-e427. 30. Hirsch FR, Kerr KM, Bunn PA Jr, et al. Molecular and immune biomarker testing in squamous-cell lung cancer: effect of current and future therapies and technologies. Clin Lung Cancer. 2018;19(4):331-339.
1L, first-line; 2L, second-line; CRT, chemoradiation therapy; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); NG, nasogastric; NSCLC, non-small cell lung cancer; po, by mouth; q3w, once every 3 weeks; qd, once daily; T790M, exon 20 threonine 790 methionine substitution. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-55578. AstraZeneca Pharmaceuticals LP. 3. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
CI, confidence interval; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
1L, first-line; AJCC, American Joint Committee on Cancer; ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; EHR, electronic health records; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; G12C, glycine-to-cysteine substitution at codon 12; HER2, human epidermal growth factor receptor; ICI, immune checkpoint inhibitor; ILD, interstitial lung disease; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; ORR, overall response rate; PD-L1, programmed death-ligand 1; QNS, quantity not sufficient; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor. References: 1. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596-609. 2. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153. 3. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Robert NJ, Espirito JL, Chen L, et al. Biomarker testing and tissue journey among patients with metastatic non-small cell lung cancer receiving first-line therapy in The US Oncology Network. Lung Cancer. 2022;166:197-204. 6. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187 [supplementary appendix 2]. 7. Data on File. US-42770. EGFR TKI prescription data from Flatiron Health EHR-derived database (included patients who started treatment between October 2017 to April 2020, all data collected online). Ipsos data © Ipsos 2020, all rights reserved. AstraZeneca Pharmaceuticals LP. 8. Oshima Y, Tanimoto T, Yuji K, Tojo A. EGFR-TKI-associated interstitial pneumonitis in nivolumab-treated patients with non-small cell lung cancer. JAMA Oncol. 2018;4(8):1112-1115. 9. Schoenfeld AJ, Arbour KC, Rizvi H, et al. Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. Ann Oncol. 2019;30(5):839-844. 10. Ohe Y, Kato T, Sakai F, et al. Real-world use of osimertinib for epidermal growth factor receptor T790M-positive non-small cell lung cancer in Japan. Jpn J Clin Oncol. 2020;50(8):909-919. 11. Yamaguchi O, Kaira K, Kawasaki T, et al. Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non-small cell lung cancer harboring EGFR mutation. Thorac Cancer. 2020;11(4):1045-1051. 12. Uchida T, Kaira K, Yamaguchi O, et al. Different incidence of interstitial lung disease according to different kinds of EGFR-tyrosine kinase inhibitors administered immediately before and/or after anti-PD-1 antibodies in lung cancer. Thorac Cancer. 2019;10(4):975-979. 13. Kotake M, Murakami H, Naito T, et al. Practical use of osimertinib in Japanese patients with EGFR T790M mutation positive advanced non-small-cell lung cancer [abstract]. Ann Oncol. 2016;27(suppl9):ix147. 14. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2023. 15. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc.; 2023. 16. Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023. 17. Yervoy [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023. 18. Libtayo [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 2023. 19. Lisberg A, Cummings A, Goldman JW, et al. A phase II study of pembrolizumab in EGFR-mutant, PD-L1+, tyrosine kinase inhibitor naïve patients with advanced NSCLC. J Thorac Oncol. 2018;13(8):1138-1145. 20. Reck M, Rodríguez-Abreu D, Robinson AG, et al; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1–positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. 21. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819-1830. 22. Langer CJ, Gadgeel SM, Borghaei H, et al; KEYNOTE-021 Investigators. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508. 23. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378(22):2078-2092. 24. Carbone DP, Reck M, Paz-Ares L, et al; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non-small-cell-lung cancer. N Engl J Med. 2017;376(25):2415-2426. 25. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-2104. 26. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate LA): an international, randomised, open-label, phase 3 trial [published correction appears in Lancet Oncol. 2021;22(3):e92]. Lancet Oncol. 2021;22(2):198-211. 27. West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(7):924-937. 28. Socinski MA, Jotte RM, Cappuzzo F, et al; IMpower150 Study Group. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. 29. Nishio M, Barlesi F, West H, et al. Atezolizumab plus chemotherapy for first-line treatment of nonsquamous NSCLC: results from the randomized phase 3 IMpower132 trial. J Thorac Oncol. 2021;16(4):653-664. 30. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med. 2020;383(14):1328-1339. 31. Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PDL1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604. 32. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022;28(11):2374-2380. 33. Johnson ML, Cho BC, Luft A, et al. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol. 2023;41(6):1213-1227. 34. Lumakras [package insert]. Thousand Oaks, CA: Amgen Inc.; 2023. 35. Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021;384(25):2371-2381. 36. Rybrevant [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2022. 37. ENHERTU [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2022. 38. Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321-1328. 39. Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321-1328 [supplemental table]. 40. D’Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95-102. 41. Dietel M, Savelov N, Salanova R, et al. Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non–small-cell lung cancer: the global, multicenter EXPRESS study. Lung Cancer. 2019;134:174-179. 42. Brown H, Vansteenkiste J, Nakagawa K, et al. Programmed cell death ligand 1 expression in untreated EGFR mutated advanced NSCLC and response to osimertinib versus comparator in FLAURA. J Thorac Oncol. 2020;15(1):138-143. 43. Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res. 2019;25(15):4691-4700. 44. Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173-180. 45. Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631-1641.
AEs, adverse events; AUC, area under the curve; BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; CR, complete response; ctDNA, circulating tumor DNA; DoR, duration of response; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; OR, odds ratio; ORR, overall response rate; OS, overall survival; PET, positron emission tomography; PFS, progression-free survival; PK, pharmacokinetics; po, by mouth; PR, partial response; PS, performance status; qd, once daily; RECIST, Response Evaluation Criteria in Solid Tumors; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Ramalingam SS, Vansteenkiste J, Planchard D, et al; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41-50. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed April 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 5. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125 [protocol]. 6. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 7. Rangachari D, Yamaguchi N, VanderLaan PA, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer. 2015;88(1):108-111. 8. Reungwetwattana T, Nakagawa K, Cho BC, et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018;36(33):3290-3297. 9. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125 [supplementary appendix]. 10. Ballard P, Yates JW, Yang Z, et al. Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130-5140. 11. Colclough N, Chen K, Johnström P, Fridén M, McGinnity DF. Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery. Drug Discov Today. 2019;24(5):1067-1073. 12. Varrone A, Varnäs K, Jucaite A, et al. A PET study in healthy subjects of brain exposure of 11C-labeled osimertinib—a drug intended for treatment of brain metastases in non-small cell lung cancer.
J Cereb Blood Flow Metab. 2020;40(4):799-807.
ALT, alanine aminotransferase; ARs, adverse reactions; AST, aspartate transaminase; CTCAE, Common Terminology Criteria for Adverse Events; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; ILD, interstitial lung disease; NCI, National Cancer Institute; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia; RTI, respiratory tract infection; TKI, tyrosine kinase inhibitor. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125.
AUC, area under the curve; BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; CTCAE, Common Terminology Criteria for Adverse Events; EGFR, epidermal growth factor receptor; FDA, US Food and Drug Administration; HR, hazard ratio; NA, not applicable; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; ORR, overall response rate; PFS, progression-free survival; po, by mouth; PS, performance status; qd, once daily; QTc, heart-rate corrected QT interval; QTcF, corrected QT interval by Fridericia; RECIST, Response Evaluation Criteria in Solid Tumors; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Mok TS, Wu YL, Ahn MJ, et al; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629-640. 3. cobas® EGFR Mutation Test v2 [package insert]. Indianapolis, IN: Roche Molecular Systems, Inc.; 2021. 4. Guardant360 CDx [package insert]. Redwood City, CA: Guardant Health, Inc.; 2023.
EGFR, epidermal growth factor receptor; IO, immunotherapy; mNSCLC, metastatic non-small cell lung cancer; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.
1L, first-line; 2L, second-line; APPs, Advanced Practice Providers; AUC, area under the curve; BCRP, breast cancer resistance protein; CRT, chemoradiotherapy; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; CYP, cytochrome P450; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; LVEF, left ventricular ejection fraction; mNSCLC, metastatic non-small cell lung cancer; NG, nasogastric; NSCLC, non-small cell lung cancer; P-GP, P-glycoprotein; q3w, once every 3 weeks; qd, once daily; QTc, heart rate-corrected QT interval; T790M, exon 20 threonine 790 methionine substitution.References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
AR, adverse reaction; AUC, area under the curve; CTCAE, Common Terminology Criteria for Adverse Events; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFRm, epidermal growth factor receptor mutation; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; po, by mouth; q3w, once every 3 weeks; qd, once daily; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia.References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Planchard D, Jänne PA, Cheng Y, et al. FLAURA2: safety and CNS outcomes of first-line osimertinib ± chemotherapy in EGFRm advanced NSCLC [oral presentation]. 2023 ESMO Congress; October 20-24, 2023; Madrid, Spain. 3. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [supplementary appendix]. 4. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. 5. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol].
1L, first-line; 2L, second-line; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; LVEF, left ventricular ejection fraction; mNSCLC, metastatic non-small cell lung cancer; NG, nasogastric; NSCLC, non-small cell lung cancer; po, by mouth; q3w, once every 3 weeks; qd, once daily; T790M, exon 20 threonine 790 methionine substitution. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-55578. AstraZeneca Pharmaceuticals LP. 3. Data on File. US-74462. AstraZeneca Pharmaceuticals LP.
AUC, area under the curve; BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; CR, complete response; ctDNA, circulating tumor DNA; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; DoR, duration of response; ECG, electrocardiogram; eCRF, electronic case-report form; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; Ex19del, exon 19 deletion; HR, hazard ratio; ILD, interstitial lung disease; L858R, exon 21 leucine 858 arginine substitution; mOS, median overall survival; mPFS, median progression-free survival; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; po, by mouth; PR, partial response; PS, performance status; q3w, once every 3 weeks; qd, once daily; RECIST, Response Evaluation Criteria in Solid Tumors; TKI, tyrosine kinase inhibitor; WHO, World Health Organization.References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. 3. Valdiviezo N, Okamoto I, Hughes BGM, et al. First-line osimertinib ± platinum-pemetrexed in EGFRm advanced NSCLC: FLAURA2 post-progression outcomes [oral presentation]. Presented at: 2024 European Lung Cancer Congress; March 20-23, 2024; Prague, Czech Republic. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Jänne PA, Planchard D, Cheng Y, et al. Osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2) [oral presentation]. Presented at: 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore. 6. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [supplementary appendix]. 7. Jänne PA, Planchard D, Kobayashi K, et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2024;42(7):808-820. 8. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol].
1L, first-line; 2L, second-line; CRT, chemoradiotherapy; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; mNSCLC, metastatic non-small cell lung cancer; NSCLC, non-small cell lung cancer; T790M, exon 20 threonine 790 methionine substitution. Reference: 1. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
AUC, area under the curve; CI, confidence interval; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; mPFS, median progression-free survival; NE, not estimable; NSCLC, non-small cell lung cancer; PFS, progression-free survival; po, by mouth; q3w, once every 3 weeks; qd, once daily. Reference: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
1L, first-line; AJCC, American Joint Committee on Cancer; ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; CI, confidence interval; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; EHR, electronic health records; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; Ex19del, exon 19 deletion; G12C, glycine-to-cysteine substitution at codon 12; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; ICI, immune checkpoint inhibitor; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; PD-L1, programmed death-ligand 1; PFS, progression-free survival; QNS, quantity not sufficient; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; SCLC, small cell lung cancer; SEER, Surveillance, Epidemiology, and End Results; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor. References: 1. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596-609. 2. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153. 3. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 12, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Robert NJ, Espirito JL, Chen L, et al. Biomarker testing and tissue journey among patients with metastatic non-small cell lung cancer receiving first-line therapy in The US Oncology Network. Lung Cancer. 2022;166:197-204. 6. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187 [supplementary appendix 2]. 7. Data on File. US-76421. AstraZeneca Pharmaceuticals LP. 8. Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321-1328. 9. Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321-1328 [supplemental table]. 10. Dietel M, Savelov N, Salanova R, et al. Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non–small-cell lung cancer: the global, multicenter EXPRESS study. Lung Cancer. 2019;134:174-179. 11. D’Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95-102. 12. Brown H, Vansteenkiste J, Nakagawa K, et al. Programmed cell death ligand 1 expression in untreated EGFR mutated advanced NSCLC and response to osimertinib versus comparator in FLAURA. J Thorac Oncol. 2020;15(1):138-143. 13. Lumakras [package insert]. Thousand Oaks, CA: Amgen Inc.; 2023. 14. Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021;384(25):2371-2381. 15. ENHERTU [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2022. 16. Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res. 2019;25(15):4691-4700. 17. Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173-180. 18. Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631-1641. 19. Peters S, Bexelius C, Munk V, Leighl N. The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer. Cancer Treat Rev. 2016;45:139-162. 20. Su PL, Wu YL, Chang WY, et al. Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer. Ther Adv Med Oncol. 2018;10:1758835918797589. 21. Koyama N, Watanabe Y, Iwai Y, et al. Distinct benefit of overall survival between patients with non-small-cell lung cancer harboring EGFR exon 19 deletion and exon 21 L858R substitution. Chemotherapy. 2017;62(3):151-158. 22. Sheng M, Wang F, Zhao Y, et al. Comparison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment: a meta-analysis. Eur J Clin Pharmacol. 2016;72(1):1-11. 23. Li J, Zhu H, Sun L, Xu W, Wang X. Prognostic value of site-specific metastases in lung cancer: a population based study. J Cancer. 2019;10(14):3079-3086. 24. Li L, Luo S, Lin H, et al. Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(8):2510-2520. 25. Rangachari D, Yamaguchi N, VanderLaan PA, et al. Brain metastases in patients with EGFR-mutated or ALK rearranged non-small-cell lung cancers. Lung Cancer. 2015;88(1):108-111.
CI, confidence interval; CRT, chemoradiation therapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; L858R, exon 21 leucine 858 arginine substitution; mPFS, median progression-free survival; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; PFS, progression-free survival; PS, performance status. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; cCRT, concurrent chemoradiation therapy; CNS, central nervous system; CRT, chemoradiation therapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase.References: 1. Park SE, Noh JM, Kim YJ, et al. EGFR mutation is associated with short progression-free survival in patients with stage III non-squamous cell lung cancer treated with concurrent chemoradiotherapy. Cancer Res Treat. 2019;51(2):493-501. 2. Kim H, Park S, Jung HA, et al. EGFR mutation–positive unresectable stage III non-squamous lung cancer is associated with a high incidence of brain metastasis. Cancer Res Treat. 2023;55(2):498-505. 3. Tanaka K, Hida T, Oya Y, et al. EGFR mutation impact on definitive concurrent chemoradiation therapy for inoperable stage III adenocarcinoma. J Thorac Oncol. 2015;10(12):1720-1725. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 6. Aggarwal C, Bubendorf L, Cooper WA, et al. Molecular testing in stage I-III non-small cell lung cancer: approaches and challenges. Lung Cancer. 2021;162:42-53. 7. Anand K, Phung TL, Bernicker EH, Cagle PT, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442.
AJCC/UICC, American Joint Committee on Cancer/Union for International Cancer Control; ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; BRAF, v-raf murine sarcoma viral oncogene homolog B1; cCRT, concurrent chemoradiation therapy; CI, confidence interval; CNS, central nervous system; CR, complete response; CRT, chemoradiation therapy; CT, computed tomography; DoR, duration of response; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; Ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; ILD, interstitial lung disease; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; mPFS, median progression-free survival; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PR, partial response; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; sCRT, sequential chemoradiation therapy; SD, stable disease; TKI, tyrosine kinase inhibitor; WHO, World Health Organization. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597. 3. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [supplementary appendix]. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Ramalingam SS, Özgüroğlu M, Ahn MJ, et al. Osimertinib after definitive chemoradiotherapy in patients with unresectable stage III EGFRm NSCLC: updated overall survival analysis from the LAURA study [oral presentation]. Presented at: European Lung Cancer Conference; March 26-29, 2025; Paris, France. 6. Lu S, Ahn MJ, Reungwetwattana T, et al. Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study. Ann Oncol. 2024;35(12):1116-1125. 7. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [protocol]. 8. Aggarwal C, Bubendorf L, Cooper WA, et al. Molecular testing in stage I-III non-small cell lung cancer: approaches and challenges. Lung Cancer. 2021;162:42-53. 9. Anand K, Phung TL, Bernicker EH, Cagle PR, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442. 10. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol].
ARs, adverse reactions; CRT, chemoradiation therapy; CTCAE, Common Terminology Criteria for Adverse Events; EGFRm, epidermal growth factor receptor mutation; ILD, interstitial lung disease; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; QTc, heart rate-corrected QT interval. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597.
ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; BRAF, v-raf murine sarcoma viral oncogene homolog B1; cCRT, concurrent chemoradiotherapy; CI, confidence interval; CNS, central nervous system; CR, complete response; CRT, chemoradiotherapy; CTCAE, Common Terminology Criteria for Adverse Events; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; Ex19del, exon 19 deletion; FDA, US Food and Drug Administration; HR, hazard ratio; ILD, interstitial lung disease; KRAS, V-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog; L858R, exon 21 leucine 858 arginine substitution; MET, mesenchymal-epithelial transition; mOS, median overall survival; mPFS, median progression-free survival; MRI, magnetic resonance imaging; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NCI, National Cancer Institute; NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PR, partial response; PS, performance status; QTc, heart rate-corrected QT interval; RECIST, Response Evaluation Criteria in Solid Tumors; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; SD, stable disease; TKI, tyrosine kinase inhibitor. References: 1. Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. 2. Bethune G, Bethune D, Ridgway N, Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010;2(1):48-51. 3. Kim H, Park S, Jung HA, et al. EGFR mutation–positive unresectable stage III non-squamous lung cancer is associated with a high incidence of brain metastasis. Cancer Res Treat. 2023;55(2):498-505. 4. Tanaka K, Hida T, Oya Y, et al. EGFR mutation impact on definitive concurrent chemoradiation therapy for inoperable stage III adenocarcinoma. J Thorac Oncol. 2015;10(12):1720-1725. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed July 10, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 7. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [protocol]. 8. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597. 9. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [supplementary appendix]. 10. Ramalingam SS, Özgüroğlu M, Ahn MJ, et al. Osimertinib after definitive chemoradiotherapy in patients with unresectable stage III EGFRm NSCLC: updated overall survival analysis from the LAURA study [oral presentation]. Presented at: European Lung Cancer Conference; March 26- 29, 2025; Paris, France. 11. Lu S, Ahn MJ, Reungwetwattana T, et al. Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study. Ann Oncol. 2024;35(12):1116-1125. 12. Aggarwal C, Bubendorf L, Cooper WA, et al. Molecular testing in stage I-III non-small cell lung cancer: approaches and challenges. Lung Cancer. 2021;162:42-53. 13. Anand K, Phung TL, Bernicker EH, Cagle PR, Olsen RJ, Thomas JS. Clinical utility of reflex ordered testing for molecular biomarkers in lung adenocarcinoma. Clin Lung Cancer. 2020;21(5):437-442. 14. Wald P, Mo X, Barney C, et al. Prognostic value of primary tumor volume changes on kV-CBCT during definitive chemoradiotherapy for stage III non–small cell lung cancer. J Thorac Oncol. 2017;12(12):1779-1787. 15. Jabbour SK, Kim S, Haider SA, et al. Reduction in tumor volume by cone beam computed tomography predicts overall survival in non-small cell lung cancer treated with chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2015;92(3):627-633.
1L, first-line; 2L, second-line; CTCAE, Common Terminology Criteria for Adverse Events; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; mNSCLC, metastatic non-small cell lung cancer; NCI, National Cancer Institute; NG, nasogastric; NSCLC, non-small cell lung cancer; QTc, heart rate-corrected QT interval; T790M, exon 20 threonine 790 methionine substitution. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Data on File. US-89546. AstraZeneca Pharmaceuticals LP.
EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; L858R, exon 21 leucine 858 arginine substitution; NSCLC, non-small cell lung cancer; PET, positron emission tomography; T790M, exon 20 threonine 790 methionine substitution; WT, wild-type. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 3. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046-1061. 4. Finlay MR, Anderton M, Ashton S, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014;57(20):8249-8267.
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