PFS

now announcing new indication

In locally advanced, unresectable stage III EGFRm NSCLC following CRT

TAGRISSO demonstrated an almost sevenfold increase in median PFS following CRT¹

TAGRISSO is the first and only targeted treatment/EGFR TKI in unresectable stage III NSCLC¹

84^%

reduction in risk of progression or death vs placebo

39.1 months mPFS with TAGRISSO
(95% CI: 31.5, NE) vs 5.6 months mPFS
with placebo (95% CI: 3.7, 7.4)
HR=0.16 (95% CI: 0.10, 0.24); P<0.001; N=216¹

PROGRESSION-FREE SURVIVAL BY BICR¹*^†

PFS RATES AT 12 MONTHS AND 24 MONTHS²

Time	TAGRISSO	Placebo
12 months	74% (95% CI: 65, 80)	22% (95% CI: 13, 32)
24 months	65% (95% CI: 56, 73)	13%(95% CI: 6, 22)

PFS rates were not powered to show
statistical significance.

Data maturity was 56% at time of analysis (120 targeted events)²
In a sensitivity analysis of PFS by investigator assessment, median PFS was 38.9 months (95% CI: 26.7, NC) for TAGRISSO and 7.3 months (95% CI: 5.5, 10.3) for placebo. HR=0.19 (95% CI: 0.12, 0.29); N=216³ — The sensitivity analysis was consistent with BICR assessment. It was not powered to show statistical significance
- The sensitivity analysis was consistent with BICR assessment. It was not powered to show statistical significance

NCCN
CATEGORY 1
RECOMMENDATION

Osimertinib (TAGRISSO) following CRT is an NCCN Category 1 recommendation for patients with unresectable stage III NSCLC who have an EGFR exon 19 deletion or exon 21 L858R mutation.^4‡§

^‡See the NCCN Guidelines^® for detailed recommendations, including other treatment options.⁴

^§Osimertinib is recommended as consolidation therapy for patients with unresectable stage III (Category 1) EGFRm (exon 19 deletion, exon 21 L858R mutation) NSCLC with PS 0-1 and no disease progression after definitive concurrent chemoradiation.⁴

LAURA study design

In locally advanced, unresectable stage III EGFRm NSCLC following CRT

TAGRISSO demonstrated consistent PFS results across most prespecified patient subgroups²

PFS RESULTS IN PRESPECIFIED PATIENT SUBGROUPS²

The exploratory analysis of prespecified patient subgroups was not powered to show statistical significance

In locally advanced, unresectable stage III EGFRm NSCLC following CRT

Interim overall survival analysis⁵

INTERIM OVERALL SURVIVAL ANALYSIS*

OS data were immature at this interim analysis (31% maturity).
The final OS analysis has not yet been formally tested for statistical significance.

Median duration of follow-up for OS (censored patients) was 42.6 months in the TAGRISSO arm and 37.5 months in the placebo arm
As crossover was allowed in LAURA, among the 69 patients who discontinued treatment in the placebo arm, 78% received subsequent treatment with TAGRISSO

*Secondary endpoint in the LAURA trial.

In locally advanced, unresectable stage III EGFRm NSCLC following CRT

Interim CNS progression-free survival results⁶

FIRST INTERIM ANALYSIS: CNS PFS RESULTS BY NEURORADIOLOGIST BICR⁶

This was a prespecified interim analysis and has not yet been tested for statistical significance.

Data maturity was 27% at the time of analysis⁶
To control for the type I error rate, a sequential multiple testing procedure was used for PFS (primary endpoint), OS, and CNS PFS. At this analysis, CNS PFS could not be formally tested for statistical significance because the interim analysis of OS data did not reach statistical significance at a maturity of 20%⁶
All patients underwent MRI brain scans at baseline and at each follow-up during the study. Tumor assessments were performed every 8 weeks until week 48, and then every 12 weeks, until BICR-assessed progression^1,6
Median duration of follow-up for CNS PFS was 24.6 months (range: 0.0, 60.6) in the TAGRISSO arm and 5.7 months (range: 0.0, 55.1) in the placebo arm⁶
CNS PFS was defined as the time from randomization until the earliest date of CNS objective disease progression or death (by any cause in the absence of CNS progression) regardless of whether the patient withdrew from randomized therapy or received another anti-cancer therapy before CNS progression⁶

In locally advanced, unresectable stage III EGFRm NSCLC following CRT

Time to distant metastases or death results⁶

EXPLORATORY ANALYSIS: TIME TO DISTANT METASTASES OR DEATH (TTDM) BY BICR⁶

This was a prespecified exploratory analysis and was not powered to show statistical significance.

TTDM was defined as the time from randomization until the first date of distant metastases or date of death in the absence of distant metastases⁶
Distant metastases were defined as any new lesions detected on a scan that were anywhere other than the lungs or regional lymph nodes according to RECIST 1.1⁶
Median duration of follow-up for TTDM in all patients was 24.8 months (range: 0.0, 60.6) in the TAGRISSO arm and 7.2 months (range: 0.0, 55.1) in the placebo arm⁶
All patients underwent MRI brain scans at baseline and at each follow-up during the study. Tumor assessments were performed every 8 weeks until week 48, and then every 12 weeks, until BICR-assessed progression^1,6

In locally advanced, unresectable stage III EGFRm NSCLC following CRT

LAURA: A global, double-blind, randomized, phase 3 trial in patients with unresectable stage III EGFRm NSCLC following concurrent or sequential CRT^1,7

Stratification factors¹

Prior chemoradiation strategy (cCRT vs sCRT)
Tumor stage prior to chemoradiation (IIIA vs IIIB/IIIC)
Region (China vs rest of the world)

Following CRT^1,7

Patients whose disease did not progress during or following CRT were eligible for randomization
After CRT completion, every patient received baseline CT scan and/or MRI ≤28 days prior to randomization
Tumor assessment at baseline, every 8 weeks until 48 weeks, then every 12 weeks until progression

Crossover from placebo to open-label TAGRISSO was allowed for patients following disease progression¹

Patients received either concurrent or sequential CRT—including ≥2 cycles every 3 weeks or 5 weekly doses of platinum-based chemotherapy and a total dose of radiation of 60 Gy±10% (54 to 66 Gy)—prior to randomization^1,7

Primary endpoint: PFS as assessed by BICR (blinded independent central review) per RECIST 1.1¹

Key secondary endpoints: OS, CNS PFS, ORR, and DoR²

Key exclusion criteria: History of ILD prior to CRT; symptomatic pneumonitis following CRT; QT prolongation or any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; any factors that increase the risk of QT prolongation; prior treatment with an EGFR TKI, chemotherapy, radiation therapy, immunotherapy, or investigational agents for NSCLC outside of that received in the definitive setting for stage III disease as part of CRT⁷

LAURA included patients with a wide range of clinicopathologic features²

LAURA PATIENT DEMOGRAPHICS

*One patient in the TAGRISSO arm underwent randomization without an approved positive local or central EGFR test result.

^†Did not meet progressive disease criteria and were not measurable after CRT.

Test every eligible patient for EGFR mutations to help target and treat the driver of disease

It is critical to test every patient with unresectable stage III NSCLC for EGFR mutations

TEST

every eligible patient for
EGFR mutations

KNOW

mutation status to help
inform treatment
decisions

TREAT

eligible patients with
unresectable stage III EGFRm
NSCLC with TAGRISSO¹

Pill image is not actual size.

Strong partnerships across the MDT as well as reflexive molecular testing have been shown to help guide
appropriate treatment for eligible patients across stages of NSCLC and can help decrease turnaround times.⁸

Adoption of reflex testing at diagnosis significantly reduced turnaround time for molecular testing results by
~37 days on average in a retrospective cohort study, including 166 newly diagnosed patients with NSCLC of any pathologic stage; P=0.0002⁹*

*Based on a single-center, retrospective study of 220 patients, including 166 patients with newly diagnosed lung adenocarcinoma whose specimens were received for molecular testing over a 3-year period between 2016 and 2018. In 2016, 39 patients had non-reflex ordered testing with an average turnaround time of 52.6 days. In 2017 and 2018, 127 patients and 54 patients, respectively, had reflex-ordered testing at diagnosis with an average turnaround time of 26.5 days and 15.6 days, respectively. Reflex-ordered biomarker testing included EGFR, KRAS, BRAF, and ERBB2 gene mutations; MET exon 14 skipping; ALK, RET, and ROS1 gene rearrangements; MET gene amplification; and PD-L1 expression by immunohistochemistry.⁹

Loading......

Eligible patients with unresectable stage III EGFRm NSCLC have an option for targeted therapy

TAGRISSO continues to address treatment gaps across the EGFRm NSCLC landscape¹

RESECTABLE
(STAGE IB-IIIA)

ADAURA

TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test¹

LOCALLY
ADVANCED,
UNRESECTABLE
(STAGE III)

LAURA

TAGRISSO is the first and only EGFR TKI 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 EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test¹

LOCALLY
ADVANCED
OR
METASTATIC

FLAURA2

TAGRISSO in combination with pemetrexed and platinum-based chemotherapy is indicated for the first-line treatment of adult patients with locally advanced* or metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test¹

*Not amenable to curative surgery or radiotherapy.¹⁰

METASTATIC
(STAGE IV)

FLAURA

TAGRISSO is indicated for the first-line treatment of adult patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test¹

See safety data for
TAGRISSO in the LAURA trial

IMPORTANT SAFETY INFORMATION

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.

You may report side effects related to AstraZeneca products .

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. 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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 KRAS^G12C 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 KRAS^G12C 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.

IMPORTANT SAFETY INFORMATION

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%

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.

You may report side effects related to AstraZeneca products .

Reference: 1. Data on File. US-74462. AstraZeneca Pharmaceuticals LP.

EGFR, epidermal growth factor receptor; IO, immunotherapy; mNSCLC, metastatic non-small cell lung cancer; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.

In locally advanced, unresectable stage III EGFRm NSCLC following CRT

TAGRISSO demonstrated an almost sevenfold increase in median PFS following CRT1

PROGRESSION-FREE SURVIVAL BY BICR1*†

PFS RATES AT 12 MONTHS AND 24 MONTHS2

TAGRISSO demonstrated consistent PFS results across most prespecified patient subgroups2

PFS RESULTS IN PRESPECIFIED PATIENT SUBGROUPS2

Interim overall survival analysis5

INTERIM OVERALL SURVIVAL ANALYSIS*

Interim CNS progression-free survival results6

FIRST INTERIM ANALYSIS: CNS PFS RESULTS BY NEURORADIOLOGIST BICR6

Time to distant metastases or death results6

EXPLORATORY ANALYSIS: TIME TO DISTANT METASTASES OR DEATH (TTDM) BY BICR6

LAURA: A global, double-blind, randomized, phase 3 trial in patients with unresectable stage III EGFRm NSCLC following concurrent or sequential CRT1,7

Stratification factors1

Following CRT1,7

LAURA included patients with a wide range of clinicopathologic features2

LAURA PATIENT DEMOGRAPHICS

Test every eligible patient for EGFR mutations to help target and treat the driver of disease

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Eligible patients with unresectable stage III EGFRm NSCLC have an option for targeted therapy

IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS

TAGRISSO demonstrated an almost sevenfold increase in median PFS following CRT¹

PROGRESSION-FREE SURVIVAL BY BICR¹*^†

PFS RATES AT 12 MONTHS AND 24 MONTHS²

TAGRISSO demonstrated consistent PFS results across most prespecified patient subgroups²

PFS RESULTS IN PRESPECIFIED PATIENT SUBGROUPS²

Interim overall survival analysis⁵

Interim CNS progression-free survival results⁶

FIRST INTERIM ANALYSIS: CNS PFS RESULTS BY NEURORADIOLOGIST BICR⁶

Time to distant metastases or death results⁶

EXPLORATORY ANALYSIS: TIME TO DISTANT METASTASES OR DEATH (TTDM) BY BICR⁶

LAURA: A global, double-blind, randomized, phase 3 trial in patients with unresectable stage III EGFRm NSCLC following concurrent or sequential CRT^1,7

Stratification factors¹

Following CRT^1,7

LAURA included patients with a wide range of clinicopathologic features²