Please see the serious Warnings and Precautions associated with TAGRISSO.

In first-line locally advanced or metastatic EGFRm NSCLC

The majority of adverse reactions in FLAURA2 were Grade 1 or 2

ADVERSE REACTIONS OCCURRING IN ≥10% OF PATIENTS IN THE FLAURA2 TRIAL¹*

Adverse Reaction	Any grade (%)	Grade 3 or higher (%)	Any grade (%)	Grade 3 or higher (%)
	TAGRISSO + CT (pem/plat) (n=276)		TAGRISSO (n=275)
Skin Disorders
Rash^†	49	2.5	44	1.5
Nail toxicity^‡	27	0.7	32	0.4
Dry skin^§	24	0	31	0
Pruritus^II	8	0	11	0
Gastrointestinal Disorders
Diarrhea	43	2.9	41	0.4
Stomatitis^¶	31	0.4	21	0.4

*NCI CTCAE v5.0.

^†Includes rash, rash erythematous, rash macular, rash maculopapular, rash papular, rash pustular, rash pruritic, rash vesicular, rash follicular, erythema, folliculitis, acne, dermatitis, dermatitis acneiform, drug eruption, skin erosion, pustule.

^‡Includes nail bed disorder, nail bed inflammation, nail bed infection, nail discoloration, nail pigmentation, nail disorder, nail toxicity, nail dystrophy, nail infection, nail ridging, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomalacia, paronychia.

^§lncludes dry skin, skin fissures, xerosis, eczema, xeroderma.

^IIIncludes pruritus, eyelid pruritus.

^¶lncludes stomatitis and mouth ulceration.

^#CT (pem/plat), pemetrexed plus platinum-based chemotherapy.

Dose modifications for adverse reactions

In first-line locally advanced or metastatic EGFRm NSCLC

Laboratory abnormalities in FLAURA2

LABORATORY ABNORMALITIES WORSENING FROM BASELINE IN ≥20% OF PATIENTS IN FLAURA2¹*^†

Laboratory Abnormality^‡	All grades (%)	Grade 3 or 4 (%)	All grades (%)	Grade 3 or 4 (%)
	TAGRISSO + CT (pem/plat) (n=276)		TAGRISSO (n=275)
Hematology
Leukopenia	88	20	53	3.3
Thrombocytopenia	85	16	44	1.8
Neutropenia	85	36	40	4.7
Lymphopenia	78	16	55	7
Chemistry
Blood creatinine increased	22	0.4	8	0

*NCI CTCAE v5.0.

^†Findings based on test results presented as CTCAE grade shifts.

^‡Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available (TAGRISSO with pemetrexed and platinum-based chemotherapy arm: 275 and TAGRISSO arm: 275).

of patients in the TAGRISSO + CT (pem/plat) arm were able to stay on treatment without discontinuation due to treatment-related ARs¹

11% of patients treated with TAGRISSO + CT (pem/plat) experienced ARs that resulted in permanent discontinuation of TAGRISSO¹

ARs that resulted in permanent discontinuation in ≥1% of patients included ILD/pneumonitis (2.9%), pneumonia (1.4%), and decreased ejection fraction (1.1%)

10% of patients treated with TAGRISSO + CT (pem/plat) experienced ARs leading to dose reductions of TAGRISSO¹

The most frequently reported adverse reactions leading to dose reduction in ≥1% of patients were diarrhea (1.1%) and rash (1.1%)

44% of patients treated with TAGRISSO + CT (pem/plat) experienced ARs leading to dose interruptions of TAGRISSO¹

ARs which required dose interruption in ≥2% of patients included anemia (4.7%), neutropenia (4.3%), diarrhea (3.6%), febrile neutropenia (3.3%), and thrombocytopenia (2.9%)

SELECT ADVERSE REACTIONS OCCURRING IN PATIENTS IN THE FLAURA2 TRIAL^1,3

Select Adverse Reaction	TAGRISSO + CT (pem/plat) (n=276)	TAGRISSO (n=275)
LOW rate of VTE (DVT or PE) 3 PE events in the TAGRISSO + CT (pem/plat) arm were fatal	0% DVT 2% PE	<1% DVT 1% PE
LOW rate of rash^* ≥ Grade 3	2.5%	1.5%
LOW rate of nail toxicity^† ≥ Grade 3, including paronychia	0.7%	0.4%
LOW reported injection site-related adverse reactions
LOW reported incidence of dry skin^‡ or pruritus^§ ≥ Grade 3

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 confirmed¹
The most common adverse reactions, including laboratory abnormalities worsening from baseline, were leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine¹
- Common adverse reactions occurring in ≥20% of patients receiving TAGRISSO + CT (pem/plat) in FLAURA2 were rash (49%), diarrhea (43%), stomatitis (31%), nail toxicity (27%), and dry skin (24%)
Clinically relevant adverse reactions in <10% of patients receiving TAGRISSO + CT (pem/plat) were alopecia (9%), epistaxis (7%), palmar-plantar erythrodysesthesia syndrome (5%), interstitial lung disease (3.3%), skin hyperpigmentation (2.5%), QTc interval prolongation (1.8%), erythema multiforme (1.4%), urticaria (1.4%), and keratitis (0.7%). QTc interval prolongation represents the incidence of patients who had a QTcF prolongation >500 msec¹
Serious adverse reactions were reported in 38% of patients treated with TAGRISSO + CT (pem/plat). The most frequently reported serious adverse reactions (≥2%) were anemia (3.3%), COVID-19 (2.5%), pneumonia (2.5%), febrile neutropenia (2.2%), thrombocytopenia (2.2%), and pulmonary embolism (2.2%)¹
Fatal adverse reactions occurred in 7% of patients who received TAGRISSO + CT (pem/plat), including pulmonary embolism (1.1%), pneumonia (1.1%), and cardiomyopathy (1.1%)¹

*Includes rash, rash erythematous, rash macular, rash maculopapular, rash papular, rash pustular, rash pruritic, rash vesicular, rash follicular, erythema, folliculitis, acne, dermatitis, dermatitis acneiform, drug eruption, skin erosion, pustule.

^†Includes nail bed disorder, nail bed inflammation, nail bed infection, nail discoloration, nail pigmentation, nail disorder, nail toxicity, nail dystrophy, nail infection, nail ridging, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomalacia, paronychia.

^‡lncludes dry skin, skin fissures, xerosis, eczema, xeroderma.

^§Includes pruritus, eyelid pruritus.

In first-line locally advanced or metastatic EGFRm NSCLC

Onset, frequency, and severity of common adverse reactions during the induction and maintenance periods

COMMON AR INCIDENCE OVER TIME IN PATIENTS ON TAGRISSO + CT (PEM/PLAT) (SAFETY ANALYSIS SET)⁴*

Common adverse reactions over time in patients on TAGRISSO + CT (pem/plat)

Includes ARs with an onset date within the study months noted, for patients still enrolled in study at the start of the respective time period⁴
At DCO (April 23, 2023), the median time of exposure was 22.3 months (range: 0.1, 33.8) in the TAGRISSO + CT (pem/plat) arm and 19.3 months (range: 0.1, 33.8) in the TAGRISSO arm^1,2

*The safety analysis set included all the patients who had undergone randomization and received at least one dose of trial treatment, according to the actual treatment received.⁴

^†Includes anemia/hemoglobin decreased.⁴

^‡Includes neutropenia/neutrophil count decreased.⁴

^§lncludes thrombocytopenia/platelet count decreased.⁴

^IIIncludes asthenia/fatigue.⁴

In first-line locally advanced or metastatic EGFRm NSCLC

In FLAURA2, patients in the TAGRISSO + CT (pem/plat) arm who discontinued platinum/pemetrexed or pemetrexed were able to continue receiving TAGRISSO⁵

Median time of exposure in the TAGRISSO + CT (pem/plat) arm^3,4,6

TAGRISSO

30.5

months (range: 0.1, 59.0)

30.5 months (range: 0.1, 59.0)

Pemetrexed (induction + maintenance)

8.3

months (range: 0.7, 58.9); patients received a median of 11 cycles (range: 1, 67)

8.3 months (range: 0.7, 58.9); patients received a median of 11 cycles (range: 1, 67)

Platinum-based chemotherapy (induction)

2.8

months (range: 0.7, 4.1); patients received a median of 4 cycles (range: 1, 6); 211 (76%) completed the planned 4 cycles

2.8 months (range: 0.7, 4.1); patients received a median of 4 cycles (range: 1, 6); 211 (76%) completed the planned 4 cycles

Median time of exposure in the TAGRISSO arm⁶

TAGRISSO

21.2

months (range: 0.1, 59.2)

21.2 months (range: 0.1, 59.2)

At data cutoff (June 12, 2025) ⁶
- In the TAGRISSO + CT (pem/plat) arm, 28% (n=76) of patients were receiving TAGRISSO and 4% (n=12) of patients were receiving ongoing pemetrexed*
- In the TAGRISSO arm, 18% (n=49) of patients were receiving ongoing TAGRISSO*
- In both arms, platinum-based CT was the most common subsequent anti-cancer treatment (44% [n=39] and 72% [n=103] in the TAGRISSO + CT (pem/plat) and TAGRISSO arms, respectively)^†

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Dosing in FLAURA2¹

TAGRISSO + CT (pem/plat) dosing
- In cycles 1-4, TAGRISSO 80 mg po qd + pemetrexed (500 mg/m²) q3w + cisplatin (75 mg/m²) or carboplatin (AUC 5) q3w; in cycles 5+, TAGRISSO 80 mg po qd + pemetrexed maintenance (500 mg/m²) q3w until disease progression or unacceptable toxicity
TAGRISSO dosing: 80 mg po qd until disease progression or unacceptable toxicity

*Includes treatment beyond progression.⁶

^†Subsequent anti-cancer treatments included those with a start date after the last dose of study treatment; patients could have received more than one subsequent anti-cancer treatment, and percentages of patients by treatment type are calculated from the number of patients who discontinued randomized study treatment.²

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; 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.

1L, first-line; 2L, second-line; AUC, area under the curve; CI, confidence interval; CRT, chemoradiation therapy; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; 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; mPFS, median progression-free survival; NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; po, by mouth; PS, performance status; 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.8.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 15, 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. 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.

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.

Reference: 1. Data on File. US-101359. 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. 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.1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed November 6, 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. 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; 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. 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. 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. 4. 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. 6. Hüyük M, Fiocco M, Postmus PE, Cohen D, von der Thüsen JH. Systematic review and meta-analysis of the prognostic impact of lymph node micrometastasis and isolated tumour cells in patients with stage I-IIIA non-small cell lung cancer. Histopathology. 2023;82(5):650-663.5. 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. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.1.2026.. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed November 6, 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. 8. 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. 9. Black RC, Khurshid H. NSCLC: an update of driver mutations, their role in pathogenesis and clinical significance. R I Med J (2013). 2015;98(10):25-28. 10. 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. 11. 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]. 12. 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. 13. 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. 14. Kidane B, Bott M, Spicer J, et al. The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: staging and multidisciplinary management of patients with early-stage non-small cell lung cancer. J Thorac Cardiovasc Surg. 2023;166(3):637-654. 15. 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. 16. 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. 17. 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. 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. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

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. J Clin Oncol. 2023;41(10):1830-1840. 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. J Clin Oncol. 2023;41(10):1830-1840 [protocol]. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.8.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 15, 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. 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. 8. 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]. 9. 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]. 10. 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. 11. 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]. 12. 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. 13. 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.

ARs, adverse reactions; CTCAE, Common Terminology Criteria for Adverse Events; NCI, National Cancer Institute; 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. Hüyük M, Fiocco M, Postmus PE, Cohen D, von der Thüsen JH. Systematic review and meta-analysis of the prognostic impact of lymph node micrometastasis and isolated tumour cells in patients with stage I-IIIA non-small cell lung cancer. Histopathology. 2023;82(5):650-663. 3. 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. 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. Kidane B, Bott M, Spicer J, et al. The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: staging and multidisciplinary management of patients with early-stage non-small cell lung cancer. J Thorac Cardiovasc Surg. 2023;166(3):637-654. 6. 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. 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. 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. 10. 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. 11. 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. 12. 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. 13. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 14. 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. J Clin Oncol. 2023;41(10):1830-1840. 15. 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. 16. 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. J Clin Oncol. 2023;41(10):1830-1840 [protocol]. 17. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.8.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 15, 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. 18. 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]. 19. 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. 20. 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]. 21. 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. 22. 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. 23. 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. 24. 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. 25. 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. 26. 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; NG, nasogastric; NSCLC, non-small cell lung cancer; 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.8.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 15, 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.

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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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. 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. 9. 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. 10. 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. 11. 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. 12. 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. 13. 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. 14. 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. 15. 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. 16. 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. 17. 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. 18. Yamaguchi O, Kaira K, Kawasaki T, et al. 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N Engl J Med. 2021;384(25):2371-2381. 45. 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. 46. 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]. 47. 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. 48. 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. 49. 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. 50. 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. 51. 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. 52. 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.8.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed August 15, 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. 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 [protocol]. 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. 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].

ALT, alanine aminotransferase; ARs, adverse reactions; AST, aspartate transaminase; CTCAE, Common Terminology Criteria for Adverse Events; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; 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; 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.

mNSCLC, metastatic non-small cell lung cancer; NSCLC, non-small cell lung cancer.

1L, first-line; 2L, second-line; APPs, Advanced Practice Providers; AUC, area under the curve; BCRP, breast cancer resistance protein; CRT, chemoradiation therapy; 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.

ARs, adverse reactions; AUC, area under the curve; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; CTCAE, Common Terminology Criteria for Adverse Events; DVT, deep vein thrombosis; EGFRm, epidermal growth factor receptor mutation; ILD, interstitial lung disease; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer; PE, pulmonary embolism; po, by mouth; q3w, once every 3 weeks; qd, once daily; QTc, heart rate-corrected QT interval; QTcF, corrected QT interval by Fridericia; VTE, venous thromboembolism. 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. 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: safety and CNS outcomes of first-line osimertinib ± chemotherapy in EGFRm advanced NSCLC [oral presentation]. Presented at: 2023 ESMO Congress; October 20-24, 2023; Madrid, Spain. 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]. 6. Jänne PA, Planchard D, Kobayashi K, et al. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC [published online ahead of print October 17, 2025]. N Engl J Med. doi: 10.1056/NEJMoa2510308.

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; NC, not calculable; NCCN, National Comprehensive Cancer Network^® (NCCN^®); NE, not estimable; NGS, next-generation sequencing; NR, not reached; 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; TP53, tumor protein 53; 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. 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. 4. Jänne PA, Planchard D, Kobayashi K, et al; FLAURA2 Investigators. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC [published online ahead of print October 17, 2025]. N Engl J Med. doi: 10.1056/NEJMoa2510308. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer V.2.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed December 2, 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. 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. Valdiviezo N, Gray JE, Jänne PA, et al. FLAURA2: Impact of tumor burden on outcomes of first-line osimertinib ± chemotherapy in patients with EGFR-mutated advanced NSCLC [oral presentation]. Presented at: World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. 8. Yang JCH, Robichaux J, Planchard D, et al. FLAURA2: Resistance, and impact of baseline TP53 alterations in patients treated with first-line osimertinib with or without platinum-pemetrexed [oral presentation]. Presented at: World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA. 9. 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. 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].

1L, first-line; AUC, area under the curve; CI, confidence interval; CT (pem/plat), pemetrexed plus platinum-based chemotherapy; EGFRm, epidermal growth factor receptor mutation; FDA, US Food and Drug Administration; HR, hazard ratio; IA, investigator assessment; L858R, exon 21 leucine 858 arginine substitution; mPFS, median progression-free survival; mOS, median overall survival; NC, not calculable; NCCN, National Comprehensive Cancer Network^® (NCCN^®); NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival; po, by mouth; q3w, once every 3 weeks; qd, once daily. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Jänne PA, Planchard D, Kobayashi K, et al. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC [published online ahead of print October 17, 2025]. N Engl J Med. doi: 10.1056/NEJMoa2510308. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer V.2.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed December 2, 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. 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.

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. 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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. 50. 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. 51. 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. 52. 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.

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; mNSCLC, metastatic non-small cell lung cancer; mPFS, median progression-free survival; 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. Reference: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

ALK, anaplastic lymphoma kinase; BRAF, v-raf murine sarcoma viral oncogene homolog B1; cCRT, concurrent chemoradiotherapy; CNS, central nervous system; CRT, chemoradiotherapy; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2; FDA, US Food and Drug Administration; 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; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; TKI, tyrosine kinase inhibitor.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.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. 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 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. 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].

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 chemoradiotherapy; CI, confidence interval; CNS, central nervous system; CR, complete response; CRT, chemoradiotherapy; 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; 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; RECIST, Response Evaluation Criteria in Solid Tumors; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1 receptor tyrosine kinase; sCRT, sequential chemoradiotherapy; SD, stable disease; TKI, tyrosine kinase inhibitor; WHO PS, World Health Organization performance status. References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Lu S, Kato T, Dong X, et al; LAURA 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 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.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. 5. Lu S, Kato T, Dong X, et al; LAURA Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [protocol]. 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 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.

ARs, adverse reactions; CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; ILD, interstitial lung disease; NCI, National Cancer Institute; 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 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; MDT, multidisciplinary team; MET, mesenchymal-epithelial transition; mPFS, median progression-free survival; NC, not calculable; NCCN, National Comprehensive Cancer Network® (NCCN®); NCI, National Cancer Institute; NE, not estimable; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1; PFS, progression-free survival; PR, partial response; 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. 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.3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed January 14, 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 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 Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597 [supplementary appendix]. 10. 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. 11.. 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. 12. 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.

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; 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.

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-101359. AstraZeneca Pharmaceuticals LP.

mNSCLC, metastatic non-small cell lung cancer; NSCLC, non-small cell lung cancer.

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; 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.

The majority of adverse reactions in FLAURA2 were Grade 1 or 2

Laboratory abnormalities in FLAURA2

of patients in the TAGRISSO + CT (pem/plat) arm were able to stay on treatment without discontinuation due to treatment-related ARs1

of patients in the TAGRISSO + CT (pem/plat) arm were able to stay on treatment without discontinuation due to treatment-related ARs1

Onset, frequency, and severity of common adverse reactions during the induction and maintenance periods

In FLAURA2, patients in the TAGRISSO + CT (pem/plat) arm who discontinued platinum/pemetrexed or pemetrexed were able to continue receiving TAGRISSO5

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IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS

of patients in the TAGRISSO + CT (pem/plat) arm were able to stay on treatment without discontinuation due to treatment-related ARs¹

of patients in the TAGRISSO + CT (pem/plat) arm were able to stay on treatment without discontinuation due to treatment-related ARs¹

In FLAURA2, patients in the TAGRISSO + CT (pem/plat) arm who discontinued platinum/pemetrexed or pemetrexed were able to continue receiving TAGRISSO⁵