In metastatic EGFRm NSCLC
More than 50% of your patients with mNSCLC of adenocarcinoma histology may have an actionable mutation*

MUTATIONS IN PATIENTS WITH mNSCLC OF ADENOCARCINOMA HISTOLOGY^1-3*

DON’T MISS A MUTATION

It is guideline recommended to test every eligible patient with mNSCLC to find if a driver of the disease exists, if clinically feasible⁴

Actionable mutations
Other driver mutations
Unknown mitogenic driver/no driver

Other driver mutations and unknown mitogenic driver/no driver pie chart

DON’T MISS A MUTATION

It is guideline recommended to test every eligible patient with mNSCLC to find if a driver of the disease exists, if clinically feasible⁴

Actionable mutations
Other driver mutations
Unknown mitogenic driver/no driver

NCCN
RECOMMENDATION

National Comprehensive Cancer Network^® (NCCN^®)
Test eligible patients with mNSCLC for targetable genetic alterations to both identify potentially efficacious targeted therapies and avoid therapies unlikely to provide clinical benefit.⁴

Test eligible patients with mNSCLC for targetable genetic alterations to both identify potentially efficacious targeted therapies and avoid therapies unlikely to provide clinical benefit.⁴

A retrospective observational study of patients with mNSCLC who initiated first-line systemic therapy revealed that:

While most patients had at least one
biomarker test performed for ALK, BRAF,
EGFR, ROS1, or PD-L1, only about 60%
of patients with nonsquamous histology had
their EGFR test results prior to initiation
of first-line therapy^5§

A retrospective observational study of patients with mNSCLC who initiated first-line systemic therapy revealed that:

While most patients had at least one biomarker
test performed for ALK, BRAF, EGFR, ROS1, or
PD-L1, only about 60% of patients with
nonsquamous histology had their EGFR test
results prior to initiation of first-line therapy^5§

*Jordan et al (2017) prospectively analyzed a total of 915 tumors from 860 patients with recurrent or metastatic lung adenocarcinoma for mutations in >300 cancer-associated genes using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, a hybridization capture-based, next-generation sequencing platform.¹

^†Gatalica et al (2019) reviewed a large cohort of solid malignancies profiled by a commercial laboratory that were tested for NTRK gene fusions and other pathogenic/targetable genomic and protein alterations. Patients’ stage of disease was not disclosed. 4073 patients in the study had non-small cell lung carcinomas of adenocarcinoma histology, of which 4 patients had an NTRK fusion.²

^‡Nassar et al (2021) extracted data from the registry of the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) version 8.0 to study the distribution of KRAS mutations in 32,138 patients with cancer across race and sex. KRAS mutations were identified in 1867 samples, most frequently in patients with NSCLC (1443 of 10,444). 76.3% of patients with NSCLC had lung adenocarcinoma histology. Patients’ stage of disease was not disclosed.^3,6

^§Based on a retrospective observational chart review study of 3474 adult patients with mNSCLC between April 2018 and March 2020. Study assessed for 5 biomarkers: EGFR, ALK, ROS1, BRAF, and PD-L1. 81.2% (2820/3474) had mNSCLC of nonsquamous histology. In patients with nonsquamous histology, 63% were tested before initiation of 1L therapy for EGFR, 63% for ALK, 73% for PD-L1, 61% for ROS1, 47% for BRAF, and 39% had all 5 biomarkers tested. Data were collected from community-based oncology practices within The US Oncology Network.⁵

In metastatic EGFRm NSCLC

Don’t assume mutation status based on smoking history, race, or gender⁷*

Test every patient with mNSCLC for actionable mutations

NCCN
RECOMMENDATION

Clinicopathologic features, such as ethnicity, smoking status, or histology, should NOT be used to select patients with mNSCLC for EGFR mutational testing.⁴

CLINICOPATHOLOGIC FEATURES IN PATIENTS WITH METASTATIC EGFRm NSCLC TREATED WITH EGFR TKIs (N=4949)⁷

History of
smoking

47^%
(n=2301)

Non-Asian

86^%
(n=3779)^†

Male

32^%
(n=1603)

*Data from Flatiron Health EHR-derived database. Included data from patients treated between December 18, 2010 and January 31, 2023.⁷

^†Calculations are based on those who specified race, and excluded the 539 patients in the study for whom race was not specified.⁷

^‡For exon 19 deletions or exon 21 L858R mutations.

In metastatic EGFRm NSCLC

Some patients with EGFRm mNSCLC may suffer from poorer prognoses

Due to the variability of patient characteristics in EGFRm mNSCLC, some patients may require different treatment options^8-11

COMMON SITES OF METASTASES ACROSS NSCLC INCLUDE¹²:

A population study identified common metastatic sites in 54,697 patients with NSCLC and SCLC from the SEER database*

In EGFRm NSCLC, the prognosis for patients with brain metastases remains poor

Patients with EGFRm NSCLC have approximately twice the risk of CNS metastases compared with patients with EGFR wild-type disease (OR=1.99)^13†

Incidence of CNS metastases nearly doubles after 3 years as disease progresses in EGFRm mNSCLC (~24% of
patients at diagnosis; ~38% of patients at 2 years; ~47% of patients at 3 years)^14‡

*Based on 54,697 patients in the SEER database diagnosed between 2010 and 2014 with primary metastatic NSCLC or SCLC and definite lung, liver, brain, and bone metastases. Information about adrenal glands and other uncommon sites of metastases was unavailable.¹²

^†Based on meta-analysis that examined the incidence of brain metastases in EGFRm or EGFR wild-type NSCLC. 8152 patients were included from 22 multinational studies. 16 studies included patients with stage IV disease. 2664 patients had an EGFR mutation.¹³

^‡Based on a retrospective US study that evaluated the frequency of brain metastases in 381 patients with advanced NSCLC. 86 of those patients had an EGFR mutation.¹⁴

EGFR mutations are common in mNSCLC

Approximately 1 in 4 patients with metastatic NSCLC may have an EGFR mutation¹*

In EGFRm mNSCLC of adenocarcinoma histology, exon 19 deletions and exon 21 L858R mutations are the most common
- 32.7% of patients with EGFRm may have an L858R mutation^*
- 52.3% of patients with EGFRm may have an exon 19 deletion^*

Patients with exon 21 L858R mutations may have poorer outcomes than patients with exon 19 deletion mutations^10,11†

In patients treated with 1L EGFR TKIs, PFS was longer in patients who had exon 19 deletions than in those who had exon 21 L858R mutations; HR=0.76 (95% CI: 0.69, 0.92); P=0.006^11‡

^†Koyama et al (2017) retrospectively analyzed the medical records of 74 patients with stage IIIB or IV NSCLC harboring common EGFR mutations, either exon 19 deletions (n=36) or L858R mutations (n=38), who were treated with gefitinib (250 mg daily) or erlotinib (150 mg daily) from February 2008 to April 2015 at a single center in Japan. Patients with Ex19del mutations experienced significant PFS benefit compared with patients who had L858R mutations; HR=0.569 (95% CI: 0.339, 0.956); P=0.031.¹⁰

^‡Sheng et al (2016) conducted a meta-analysis of 26 randomized clinical trials that included 4835 patients; among them, 1710 patients with exon 19 deletions and 1271 patients with exon 21 L858R mutations. 17 trials were performed in first-line settings, and 9 trials in mix-line settings. Among the 26 studies, 8 first-line trials investigated efficacy of EGFR TKIs (3 gefitinib, 3 erlotinib, and 2 afatinib) vs chemotherapy on PFS and OS.¹¹

In metastatic EGFRm NSCLC, start with guideline-recommended targeted therapy

Sequential IO followed by EGFR TKI monotherapy could harm patients with EGFRm mNSCLC*

Immunotherapy (IO) is not an appropriate first-line choice in patients with certain EGFR mutations^†

Not sequentially safe

Treatment with certain EGFR TKI monotherapy after IO may increase risk of toxicity^15-20*
Not indicated

First-line indications for IO exclude patients with EGFR mutations in mNSCLC^21-25
Not targeted therapy

IO does not target the driver of disease
Not effective

In a study of first-line IO in treatment-naïve patients with EGFRm NSCLC, ORR was 0%^{26^‡}

Fourteen large and robust first-line IO trials excluded patients with EGFRm NSCLC^27-40§||

*Based on 6 studies of 3867 patients with NSCLC and EGFR sensitizing mutations. Of the 3867 patients, 395 were treated with immunotherapy followed by EGFR TKIs. Adverse reactions, including ILD, were observed following the sequential use of IO followed by EGFR-TKI therapy in patients who had EGFR mutations. Increased risk of toxicity was primarily observed with osimertinib.^15-20

^†Not applicable to patients with a KRAS G12C or ERBB2 (HER2) mutation without another actionable mutation or patients with certain EGFR exon 20 insertion mutations.^41-44

^‡Phase 2, single-arm study of pembrolizumab in patients with advanced EGFRm NSCLC. 82% of the enrolled patients were treatment naïve. The trial was stopped due to lack of efficacy after 11 of the 25 planned patients were enrolled. No responses were observed in 10 of the 11 patients treated, even in patients with PD-L1 expression ≥50%. The patient who did have a response was revealed to be EGFR wild-type upon repeat analysis.²⁶

^§KEYNOTE-024, KEYNOTE-042, KEYNOTE-021 Cohort G, KEYNOTE-189, CHECKMATE 026, CHECKMATE 227, CHECKMATE 9LA, IMpower110, IMpower130, IMpower132, IMpower150, POSEIDON, EMPOWER-Lung 1, and EMPOWER-Lung 3 did not allow patients with metastatic NSCLC with EGFR mutations. In the IMpower130 and IMpower150 trials, patients with EGFRm NSCLC were allowed only after progression on EGFR-TKI therapy or intolerance to EGFR-TKI treatment. There are no head-to-head trials comparing IO and EGFR TKIs in patients with EGFR mutation-positive mNSCLC.^27-40

^||Excluded patients with mNSCLC who had EGFR sensitizing mutations (exon 19 deletions and exon 21 L858R mutations).^27-40

In metastatic EGFRm NSCLC

PD-L1 positive may not mean EGFRm negative

PD-L1 expression may be common in patients with EGFRm

OVERLAP OF EGFR MUTATIONS AND PD-L1 EXPRESSION^45-49¶

Up to 70^%

of patients with EGFRm mNSCLC also express PD-L1 at levels >1%

Up to 70%

of patients with EGFRm NSCLC also express PD-L1 at levels >1%

NCCN
RECOMMENDATION

TARGETED THERAPY TAKES PRECEDENCE: Treatment with targeted therapy should take precedence over treatment with immunotherapy in patients with mNSCLC and certain oncogenic drivers in the first-line setting, even when PD-L1 expression levels are elevated.⁴**

TEST FIRST: Patients with mNSCLC and PD-L1 expression levels ≥1% should be confirmed negative for certain driver mutations, including EGFR exon 19 deletions and exon 21 L858R mutations, before they are treated with immune checkpoint inhibitors, if clinically feasible.^4#
TARGETED THERAPY TAKES PRECEDENCE:Treatment with targeted therapy should take precedence over treatment with immunotherapy in patients with mNSCLC and certain oncogenic drivers in the first-line setting, even when PD-L1 expression levels are elevated.⁴**

^#The NCCN Guidelines® for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays or commercial laboratories.⁴

**Not applicable to patients with a KRAS G12C or ERBB2 (HER2) mutation without another actionable mutation.^41-44

^¶Mazieres et al (2019) was a multicenter, international, retrospective study of 551 patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. 125 patients had an EGFR mutation.⁴⁵ D'Incecco et al (2015) was a multicenter, retrospective, Italian study that assessed PD-L1 expression in 125 patients with mNSCLC and EGFR mutations, ALK translocations, or KRAS mutations. 56 patients had an EGFR mutation.⁴⁷ Dietel et al (2019) was a multicenter, international, retrospective study that examined PD-L1 expression in 2368 tumor samples with histologically confirmed stage IIIB/IV primary NSCLC as classified by AJCC 7th edition. 448 patients had an EGFR mutation.⁴⁸ Brown et al (2020) analyzed PD-L1 expression in 231 samples of untreated EGFR-mutated advanced NSCLC.⁴⁹

^††EGFR sensitizing mutations (exon 19 deletions and exon 21 L858R mutations).⁴

^‡‡If an EGFR mutation is discovered during first-line therapy and there is a good response to current therapy, it is reasonable to continue therapy.

In metastatic EGFRm NSCLC

Use a comprehensive testing approach to identify every eligible patient with actionable mutations

NCCN
RECOMMENDATION

For eligible patients with metastatic NSCLC⁴

Combinations of tissue and plasma testing, either concurrently or in sequence, are acceptable*
Concurrent testing can improve time to test results and should be considered in the appropriate clinical situation

For eligible patients with metastatic NSCLC⁴

Combinations of tissue and plasma testing, either concurrently or in sequence, are acceptable*
Concurrent testing can improve time to test results and should be considered in the appropriate clinical situation

*Negative results by one method suggest the use of a complementary method. Treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.⁴

Use liquid biopsy to overcome the barriers of tissue testing^50,51

Reduce turnaround time

Liquid biopsy offers results in roughly half the time—9 days vs 15 days for tissue^†
Do more when retrieving tissue is not feasible

~23% were found to have actionable mutations with liquid biopsy^‡§
Address cases of tissue QNS

~28% were found to have actionable mutations with liquid biopsy^‡||
Find more actionable mutations

In a clinical study, detection of actionable mutations increased from 20.5% to 35.8% when liquid biopsy was added to tissue testing^‡¶

Positive liquid biopsy results are sufficient to inform treatment selection.

Negative liquid biopsy results should be reflexed to tissue biopsy.⁵²

^†Multicenter North American study of 282 patients with stage IIIB or stage IV NSCLC using next-generation sequencing as the testing platform. ~98% of patients had stage IV disease. Turnaround time is for next-generation sequencing.⁵⁰

^‡From a single-center, prospective cohort study of 323 patients with histologically confirmed stage IV NSCLC who had plasma testing as part of routine clinical management.⁵¹

^§5 out of 22 (23%) patients whose tissue was not able to be retrieved for biopsy were found to have actionable mutations through liquid biopsy only.⁵¹

^||22 out of the 79 (28%) patients who did not have sufficient quality/quantity of DNA were found to have targetable mutations via liquid biopsy.⁵¹

^¶Patients had plasma testing as part of routine clinical management.⁵¹

In metastatic EGFRm NSCLC

Per NCCN Guidelines: Test, Confirm, Treat⁴

TEST

eligible patients with mNSCLC for targetable genetic alterations to both identify potentially efficacious targeted therapies and avoid therapies unlikely to provide clinical benefit
CONFIRM

that patients with mNSCLC and PD-L1 expression levels ≥1% are confirmed negative for certain driver mutations, including EGFR (exon 19 deletion and exon 21 L858R), ALK, ROS1, BRAF, NTRK 1/2/3, RET, and MET exon 14 skipping mutations, before they are treated with immune checkpoint inhibitors*^†
TREAT

EGFRm mNSCLC patients with an EGFR TKI. Treatment with targeted therapy should take precedence over treatment with IO in patients with mNSCLC and certain oncogenic drivers in a first-line setting, even when PD-L1 expression levels are elevated

Pill image is not actual size.

*The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays or commercial laboratories.⁴

^†Not applicable to patients with a KRAS G12C or ERBB2 (HER2) mutation without another actionable mutation or patients with certain EGFR exon 20 insertion mutations.^41-44

Explore the data for TAGRISSO in metastatic EGFRm NSCLC

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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. References: 1. Data on File. US-106658. AstraZeneca Pharmaceuticals LP. 2. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

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-106658. AstraZeneca Pharmaceuticals LP. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 13, 2026. 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.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 13, 2026. 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):1755-1761. 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. 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. 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. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 13, 2026. 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.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 13, 2026. 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. 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. 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. 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.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 13, 2026. 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-106658. 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.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 13, 2026. 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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Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604. 39. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022;28(11):2374-2380. 40. Johnson ML, Cho BC, Luft A, et al. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol. 2023;41(6):1213-1227. 41. Lumakras [package insert]. Thousand Oaks, CA: Amgen Inc.; 2025. 42. Rybrevant [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2025. 43. ENHERTU [package insert]. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2025. 44. 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. 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.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed March 13, 2026. 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.

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-106658. 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 [supplementary appendix]. 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. 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].

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; 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. 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.7.2025. © 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. 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. 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; 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; 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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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.

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.

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.

In metastatic EGFRm NSCLC More than 50% of your patients with mNSCLC of adenocarcinoma histology may have an actionable mutation*

Don’t assume mutation status based on smoking history, race, or gender7*

Some patients with EGFRm mNSCLC may suffer from poorer prognoses

EGFR mutations are common in mNSCLC

Sequential IO followed by EGFR TKI monotherapy could harm patients with EGFRm mNSCLC*

PD-L1 positive may not mean EGFRm negative

Use a comprehensive testing approach to identify every eligible patient with actionable mutations

Per NCCN Guidelines: Test, Confirm, Treat4

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IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS

In metastatic EGFRm NSCLC
More than 50% of your patients with mNSCLC of adenocarcinoma histology may have an actionable mutation*

Don’t assume mutation status based on smoking history, race, or gender⁷*

Per NCCN Guidelines: Test, Confirm, Treat⁴