In resectable NSCLC

Undetectable micrometastases that drive recurrence may remain after complete resection

Despite successful surgery, micrometastases may remain¹

MOST COMMON SITES OF METASTASIS AFTER RESECTION IN NSCLC^1,2*

Brain:
~41^% Lung:
~33^% Liver:
~13^% Bone:
~24^%

Recurrence rates remain high

A retrospective analysis found that approximately 20% to 52% of patients with resected stage I-IIIA NSCLC recur within 6 years, whether or not they receive adjuvant therapy, including chemotherapy, radiation, or both^3†

A systematic review and meta-analysis of 15 studies analyzed the prognostic impact of lymph node micrometastases/isolated tumor cells (ITCs) postresection in patients with stage I-IIIA NSCLC^4‡§

DFS RATE AT 5 YEARS⁴

in patients with
lymph node micrometastases/ITCs

53^%

in patients without
lymph node micrometastases/ITCs

75^%

OS RATE AT 5 YEARS⁴

in patients with
lymph node micrometastases/ITCs

55^%

in patients without
lymph node micrometastases/ITCs

75^%

Surgical resection or radiation alone may be insufficient⁵

5-YEAR RECURRENCE OR DEATH
RATES IN STAGE IB-III NSCLC^4‡

STAGE IB

45^% (N=1371)

STAGE II

62^% (N=1616)

STAGE III^§

76^% (N=1247)

Patients received surgery, and if indicated, adjuvant therapy (chemotherapy and/or radiation)

*Chouaid et al (2018) conducted a retrospective observational study in 831 patients with complete resection of stage IB-IIIA NSCLC with no information on EGFRm status. Of the 831 patients, 200 experienced metastatic recurrence during the observed study follow-up period.²

^†Based on a single-center retrospective review of 1640 patients who had undergone resection for stage I-IIIA NSCLC from a prospectively maintained database to compare patterns of recurrence. 181 of 346 patients with stage IIIA NSCLC (52%) and 257 of 1294 patients with stage I-II NSCLC (20%) developed recurrences. Staging was based on the 7th edition of the AJCC tumor, node, and metastasis classification of lung cancer.³

^‡Hüyük et al (2023) conducted a systematic review and meta-analysis extracting DFS and OS data from 15 studies with a total of 1893 patients with stage I-IIIA NSCLC, with and without occult lymph node micrometastasis/isolated tumor cells, after surgical resection. Meta-analyses for OS and DFS were performed on 14 and 8 studies, respectively. Survival probabilities for OS and DFS at different timepoints were extracted from published survival curves. OS probabilities were reported at every 6 months after surgery until 5-year follow-up for both micrometastasis and no micrometastasis. DFS was reported at every 3 months after surgery for the first 2-year follow-up, and at every 6 months after 2 years of follow-up until 5 years of follow-up.⁴

^§According to the American Joint Committee on Cancer, micrometastases are defined as clusters of tumor cells measuring between 0.2 mm and 2.0 mm in greatest diameter, and ITCs are defined as single tumor cells or small clusters of cells, smaller than 0.2 mm in greatest diameter.⁶

In resectable EGFRm NSCLC

EGFR mutations occur across stages I-III of NSCLC, driving tumor growth

Up to 1 in 5 patients may have EGFRm NSCLC^7,8*

EGFR prevalence rates across stage I-III NSCLC: stage I, 20% (19.0, 20.4); stage II, 18% (14.9, 19.9); stage III, 18% (17.4, 17.7)

Distant metastatic recurrence in patients with stage I-III NSCLC who recurred^9†

97^%

EGFRm

72^%

Wild-type

(P=0.007)^‡

A retrospective analysis found that, of patients who recurred, significantly more patients with EGFR mutation–positive (EGFRm) NSCLC had a distant metastatic recurrence vs patients with wild-type disease
Nonmetastatic recurrence: 3% vs 28% of patients, respectively

CNS metastases are a prevalent risk in NSCLC, especially for patients with EGFRm disease^10§

Patients with EGFRm NSCLC have approximately twice the risk of CNS metastases vs patients with EGFR wild-type disease (OR=1.99)^10§

*Prevalence of EGFR mutations in NSCLC adenocarcinoma was based on data from 2 references: Sholl et al (2015) performed mutation analysis on 1007 cases with confirmed diagnosis of lung adenocarcinoma. Testing was performed on 987 cases for EGFR sensitizing mutations (exon 19 deletions, EGFR L858R mutations, EGFR G719X mutations, EGFR L861Q mutations) and other EGFR mutations (any one or more mutations in EGFR other than exon 19 deletions, L858R mutations, G719X mutations, or L861Q mutations). Out of 987 cases, 331 cases that were analyzed had stage I-III NSCLC and 632 had stage IV NSCLC. D’Angelo et al (2012) analyzed tumor specimens from a cohort of 1118 patients with stage I-III surgically resected lung adenocarcinomas with EGFR exon 19 deletions and L858R mutations only.^7,8,11,12

^†Based on a single-center, retrospective study of 282 patients with early or locally advanced lung adenocarcinoma; 142 were EGFRm and 140 were EGFR wild-type. The majority of both groups received standard-of-care treatment. Standard-of-care was defined as surgery or RT + cytotoxic platinum-based doublet therapy when appropriate.⁹

^‡Overall recurrence across all stages was ~23% in patients who were EGFRm and ~21% in patients who were EGFR wild-type. P-value corresponds to data calculation 21/29=0.72 and 31/32=0.97. The P-value of 0.007 was for the overall population (stage I-III). The only P-value by stage that was significant was for stage I (P=0.02).⁹

^§Based on a 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.¹⁰

In resectable EGFRm NSCLC

TAGRISSO DATA

reinforce that the unprecedented is possible

Initial DFS analysis: 80% reduced risk of recurrence or death
vs control arm in stage IB-IIIA; HR=0.20 (95% CI: 0.15, 0.27); P<0.0001; N=682. Median DFS was not reached (95% CI: NE, NE) for TAGRISSO and was 27.5 months (95% CI: 22.0, 35.0) for control arm.¹⁴*^†

UPDATED DFS DATA WITH ADDITIONAL 2 YEARS OF FOLLOW-UP

(Prespecified exploratory analysis)

>5
years

median disease-free survival
in patients with resected stage IB-IIIA EGFRm NSCLC
HR=0.27 (95% CI: 0.21, 0.34); N=682.¹⁵

DFS rates in patients with stage IB-IIIA EGFRm NSCLC¹⁵

2 YEARS 90^% TAGRISSO 55^% Placebo
3 YEARS 85^% TAGRISSO 44^% Placebo
4 YEARS 73^% TAGRISSO 38^% Placebo

Median time of total treatment exposure at updated DFS data cutoff was 35.8 months in the adjuvant TAGRISSO arm and 25.1 months in the placebo arm¹⁵

Osimertinib (TAGRISSO) is the first and only EGFR TKI recommended by NCCN Guidelines as an adjuvant treatment option for completely resected stage IB-IIIA EGFRm (exon 19 deletion, L858R) NSCLC.^17‡§

^‡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.¹⁷

^§Osimertinib is recommended for patients with completely resected stage IB-IIIA, stage IIIB (T3, N2), EGFR (exon 19 deletion, exon 21 L858R) NSCLC who received previous adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy.¹⁷

In the treatment of resectable EGFRm NSCLC

Target the driver of disease

The only adjuvant targeted treatment to significantly extend DFS and now OS¹³

INITIAL DFS ANALYSIS: In resected stage IB-IIIA, median DFS was not reached (95% CI: NE, NE) for TAGRISSO vs 27.5 months (95% CI: 22.0, 35.0) for placebo; HR=0.20 (95% CI: 0.15, 0.27); P<0.0001; N=682.¹³*

INITIAL DFS ANALYSIS: In resected stage IB-IIIA, median DFS was not reached (95% CI: NE, NE) for TAGRISSO vs 27.5 months (95% CI: 22.0, 35.0) for placebo; HR=0.20 (95% CI: 0.15, 0.27); P<0.0001; N=682.¹³*

Disease-free survival

in resected stage IB-IIIA^14†

UPDATED DFS ANALYSIS

>5 years median DFS

65.8 months (95% CI: 61.7, NC) median DFS for TAGRISSO

and 28.1 months (95% CI: 22.1, 35.0) for placebo

65.8 months (95% CI: 61.7, NC)
median DFS for TAGRISSO and 28.1 months
(95% CI: 22.1, 35.0) for placebo

HR=0.27 (95% CI: 0.21, 0.34); N=682

• The updated DFS analysis was a prespecified exploratory endpoint and was not powered to show statistical significance

Overall survival in resected stage IB-IIIA^13‡

Statistically significant OS

51^%

reduced risk of death

vs placebo

HR=0.49 (95% CI: 0.34, 0.70); P<0.0001; N=682

• Median OS was not reached in either TAGRISSO or placebo arm

Unprecedented improvement in OS in patients with resected stage IB-IIIA EGFRm NSCLC¹³

The only adjuvant targeted treatment proven to significantly extend survival after resection

51%

reduced risk of death
vs placebo in resected stage IB-IIIA
HR=0.49 (95% CI: 0.34, 0.70); P<0.0001; N=682¹³ Median OS: NR in either arm

OS IN RESECTED STAGE IB-IIIA
EGFRm NSCLC^13,15‡§

51^% reduced risk of death vs placebo¹

88^% OS rate at 5 years with TAGRISSO
(95% CI: 83, 91)¹⁵

OS IN RESECTED STAGE IB-IIIA EGFRm NSCLC:

Median OS: NR in either TAGRISSO or placebo arm¹³
Subsequent therapy with open-label TAGRISSO was offered to eligible patients in the placebo arm who recurred^16||
Median follow-up: 61.5 months for TAGRISSO (censored patients) and 61.5 months for placebo (censored patients). All patients have completed or discontinued study treatment¹³

OS IN RESECTED STAGE II-IIIA EGFRm NSCLC:

OS HR: 0.49 (95% CI: 0.33, 0.73); P=0.0004; n=470^13‡¶

Median OS: NR in either TAGRISSO or placebo arm¹³
Median follow-up: 61.7 months for TAGRISSO (censored patients) and 60.4 months for placebo (censored patients). All patients have completed or discontinued study treatment¹⁵

Osimertinib (TAGRISSO) is the first and only EGFR TKI with an NCCN Category 1 recommendation for adjuvant treatment following surgical resection in patients with EGFRm (exon 19 deletion, L858R mutation) NSCLC and is recommended for a duration of 3 years.^17#**

^#See the NCCN Guidelines for detailed recommendations, including other treatment options.

**Osimertinib is recommended following surgical resection in patients with EGFRm (exon 19 deletion, L858R mutation) NSCLC who received previous adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy.¹⁷

*Secondary endpoint in the ADAURA initial analysis. Primary endpoint in the initial analysis at 2 years was DFS in stage II-IIIA patients. Median DFS was not reached for TAGRISSO (95% CI: 38.8, NE) vs 19.6 months (95% CI: 16.6, 24.5) for placebo (HR=0.17 [95% CI: 0.12, 0.23]; P<0.0001).^13,15

^†Secondary endpoint in the ADAURA trial with 2 additional years of follow-up. Primary endpoint in the updated analysis was DFS in stage II-IIIA patients; median DFS was 65.8 months for TAGRISSO (95% CI: 54.4, NC) and was 21.9 months (95% CI: 16.6, 27.5) for placebo (HR=0.23 [95% CI: 0.18, 0.30]).¹⁴

^‡Secondary endpoint in ADAURA.¹³

^§OS maturity was 18% (TAGRISSO; 12%, placebo; 24%).¹⁵

^||One hundred eighty-four patients in the placebo arm received a subsequent therapy. Of these patients, 88% (n=162) received an EGFR TKI, most frequently TAGRISSO (43%; n=79).^15,18

^¶OS maturity was 21% (TAGRISSO; 15%, placebo; 27%).¹⁵

ADAURA study design

*Secondary endpoint in the initial analysis. Primary endpoint in initial analysis at 2 years was DFS in patients with resected stage II-IIIA EGFRm NSCLC. Median DFS was not reached for TAGRISSO (95% CI: 38.8, NE) and was 19.6 months (95% CI: 16.6, 24.5) for control arm (HR=0.17 [95% CI: 0.12, 0.23]; P<0.0001).¹⁴

^†Control arm=placebo.

UPDATED DFS ANALYSIS

Resectable EGFRm NSCLC

Adjuvant TAGRISSO: Consistent DFS results across all prespecified patient subgroups

Reduced risk of recurrence or death across all prespecified subgroups¹⁵*

UPDATED DFS
ANALYSIS

Updated analysis: Consistent DFS results with/without prior adjuvant chemo in resected stage IB-IIIA^14,15§||

In ADAURA, patients without prior adjuvant chemotherapy were treated as follows^14¶#:

HR0.36

(95% CI: 0.24, 0.55)¹⁵

Extend the benefits of adjuvant therapy to more patients with TAGRISSO

In ADAURA, patients with prior adjuvant chemotherapy were treated as follows^14#**:

HR0.29

(95% CI: 0.21, 0.39)¹⁵

Rethink adjuvant treatment: If you start with chemotherapy, discuss completing treatment with TAGRISSO for eligible patients with EGFRm NSCLC

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In resectable EGFRm NSCLC

OS results across prespecified patient subgroups¹⁸

OVERALL SURVIVAL RESULTS IN PRESPECIFIED PATIENT SUBGROUPS¹⁸

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

*Prespecified exploratory analysis using the updated DFS data cutoff. Median follow-up for DFS in all patients was 44.2 months for TAGRISSO and 27.7 months for placebo arm.¹⁵

^†Stage IB-IIIA.

^‡AJCC 7th edition.

^§Secondary endpoint in the updated DFS analysis (DFS in stage IB-IIIA patients): HR=0.27 (95% CI: 0.21, 0.34); N=682.¹⁵

^||In ADAURA, delivery of adjuvant chemotherapy was allowed, but not mandatory, and was decided by the physician and patient prior to study enrollment.¹⁸

^¶Exploratory subgroup analysis. In patients who did not receive prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 10 weeks.¹⁴

^#In the ADAURA trial, patients received adjuvant TAGRISSO for up to 3 years or until disease recurrence or unacceptable toxicity.¹⁴

**Exploratory subgroup analysis. In patients who received prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 26 weeks.¹⁴

Adjuvant TAGRISSO reduced the risk of death in most prespecified subgroups, including patients 65 years of age or older¹⁸

reduced risk of death
with TAGRISSO¹⁸
HR=0.42 (95% CI: 0.24, 0.69); n=302

*Prespecified exploratory analysis using the updated DFS data cutoff. Median follow-up for DFS in all patients was 44.2 months for TAGRISSO and 27.7 months for placebo arm.¹⁵

^†Stage IB-IIIA.

^‡AJCC 7th edition.

^§Secondary endpoint in the updated DFS analysis (DFS in stage IB-IIIA patients): HR=0.27 (95% CI: 0.21, 0.34); N=682.¹⁵

^||In ADAURA, delivery of adjuvant chemotherapy was allowed, but not mandatory, and was decided by the physician and patient prior to study enrollment.¹⁸

^¶Exploratory subgroup analysis. In patients who did not receive prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 10 weeks.¹⁴

^#In the ADAURA trial, patients received adjuvant TAGRISSO for up to 3 years or until disease recurrence or unacceptable toxicity.¹⁴

**Exploratory subgroup analysis. In patients who received prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 26 weeks.¹⁴

UPDATED DFS ANALYSIS

Patients with resected stage IB-IIIA EGFRm NSCLC

TAGRISSO demonstrated consistent OS results with or without prior adjuvant chemotherapy^15§

UPDATED DFS
ANALYSIS

WITHOUT PRIOR ADJUVANT CHEMOTHERAPY^II

In ADAURA, patients without prior adjuvant chemotherapy were treated as follows^13||:

TAGRISSO Without Prior Adjuvant Chemotherapy

HR0.47

(95% CI: 0.25, 0.83)¹⁵

Exploratory subgroup analysis was not powered to show statistical significance. In ADAURA, patients without prior adjuvant chemotherapy were treated with surgery, followed by TAGRISSO^13§II

Exploratory subgroup analysis was not powered to show statistical significance. In ADAURA, patients without prior adjuvant chemotherapy were treated with surgery, followed by TAGRISSO^13§II

WITH PRIOR ADJUVANT CHEMOTHERAPY^#

In ADAURA, patients with prior adjuvant chemotherapy were treated as follows^13II:

HR0.49

(95% CI: 0.30, 0.79)¹⁵

Exploratory subgroup analysis was not powered to show statistical significance. In ADAURA, patients with prior adjuvant chemotherapy were treated with surgery, followed by chemotherapy, followed by TAGRISSO^13¶#

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*Prespecified exploratory analysis using the updated DFS data cutoff. Median follow-up for DFS in all patients was 44.2 months for TAGRISSO and 27.7 months for placebo arm.¹⁵

^†Stage IB-IIIA.

^‡AJCC 7th edition.

^§Secondary endpoint in the updated DFS analysis (DFS in stage IB-IIIA patients): HR=0.27 (95% CI: 0.21, 0.34); N=682.¹⁵

^||In ADAURA, delivery of adjuvant chemotherapy was allowed, but not mandatory, and was decided by the physician and patient prior to study enrollment.¹⁸

^¶Exploratory subgroup analysis. In patients who did not receive prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 10 weeks.¹⁴

^#In the ADAURA trial, patients received adjuvant TAGRISSO for up to 3 years or until disease recurrence or unacceptable toxicity.¹⁴

**Exploratory subgroup analysis. In patients who received prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 26 weeks.¹⁴

Although prior adjuvant chemotherapy use was allowed, it was not required in the ADAURA trial¹⁹

PRIOR ADJUVANT CHEMOTHERAPY USE IN ADAURA BY STAGE²⁰

Characteristic	TAGRISSO	Placebo
Stage IB	25% (n=27)	28% (n=30)
Stage II	70% (n=80)	73% (n=85)
Stage IIIA	81% (n=95)	78% (n=92)

*Prespecified exploratory analysis using the updated DFS data cutoff. Median follow-up for DFS in all patients was 44.2 months for TAGRISSO and 27.7 months for placebo arm.¹⁵

^†Stage IB-IIIA.

^‡AJCC 7th edition.

^§Secondary endpoint in the updated DFS analysis (DFS in stage IB-IIIA patients): HR=0.27 (95% CI: 0.21, 0.34); N=682.¹⁵

^||In ADAURA, delivery of adjuvant chemotherapy was allowed, but not mandatory, and was decided by the physician and patient prior to study enrollment.¹⁸

^¶Exploratory subgroup analysis. In patients who did not receive prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 10 weeks.¹⁴

^#In the ADAURA trial, patients received adjuvant TAGRISSO for up to 3 years or until disease recurrence or unacceptable toxicity.¹⁴

**Exploratory subgroup analysis. In patients who received prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 26 weeks.¹⁴

*Stage IB-IIIA population.¹⁸

^†Based on AJCC 7th edition.¹⁵

^‡In ADAURA, delivery of adjuvant chemotherapy was allowed, but not mandatory, and was decided by the physician and patient prior to study enrollment. 60% of patients received prior adjuvant chemotherapy (adjuvant TAGRISSO arm: stage IB, 25%; stage II, 70%; stage IIIA, 81%; placebo arm: stage IB, 28%; stage II, 73%; stage IIIA, 78%).^19,20

^¶In the ADAURA trial, patients received adjuvant TAGRISSO for up to 3 years or until disease recurrence or unacceptable toxicity.¹²

^§OS results for overall patient population (completely resected stage IB-IIIA EGFRm NSCLC): median OS was not reached in either arm (HR=0.49 [95% CI: 0.34, 0.70]; P<0.0001).¹³

^IIIn patients who did not receive prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 10 weeks.¹³

^#In patients who received prior adjuvant chemotherapy in ADAURA, the interval between surgery and adjuvant TAGRISSO was up to 26 weeks.¹³

^**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.¹³

Please see the serious Warnings and Precautions associated with TAGRISSO.

In resectable EGFRm NSCLC

Adjuvant TAGRISSO: The majority of adverse reactions in ADAURA were Grade 1 or 2¹³

The safety profile in ADAURA was consistent with the established profile

ADVERSE REACTIONS OCCURRING IN ≥10% OF PATIENTS RECEIVING TAGRISSO IN ADAURA¹³*

Adverse Reactions	All grades (%)	Grade 3 or higher^† (%)	All grades (%)	Grade 3 or higher^† (%)
	TAGRISSO (n=337)		Placebo (n=343)
Gastrointestinal Disorders
Diarrhea^‡	47	2.4	20	0.3
Stomatitis^§	32	1.8	7	0
Abdominal pain^\|\|	12	0.3	7	0
Skin Disorders
Rash^¶	40	0.6	19	0
Nail toxicity^#	37	0.9	3.8	0
Dry skin**	29	0.3	7	0
Pruritus^††	19	0	9	0
Respiratory, Thoracic, and Mediastinal Disorders
Cough^‡‡	19	0	19	0
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain^§§	18	0.3	25	0.3
Infection and Infestation Disorders
Nasopharyngitis	14	0	10	0
Upper respiratory tract infection	13	0.6	10	0
Urinary tract infection^\|\|\|\|	10	0.3	7	0
General Disorders and Administration Site Conditions
Fatigue^¶¶	13	0.6	9	0.3
Nervous System Disorders
Dizziness^##	10	0	9	0
Metabolism and Nutrition Disorders
Decreased appetite	13	0.6	3.8	0

Clinically relevant adverse reactions in ADAURA that occurred in <10% of patients receiving TAGRISSO were alopecia (6%), epistaxis (6%), interstitial lung disease (3%), palmar-plantar erythrodysesthesia syndrome (1.8%), skin hyperpigmentation (1.8%), urticaria (1.5%), keratitis (0.6%), QTc interval prolongation (0.6%), and erythema multiforme (0.3%). QTc interval prolongation represents the incidence of patients who had a QTcF prolongation >500 msec¹³
Discontinuation and dose reduction rates due to ARs with TAGRISSO were 11% and 9%, respectively¹³
- The most frequent adverse reactions leading to discontinuation of TAGRISSO were interstitial lung disease (2.7%) and rash (1.2%)
- The most frequent adverse reactions leading to dose reductions or interruptions were diarrhea (4.5%), stomatitis (3.9%), nail toxicity (1.8%), and rash (1.8%)

Discontinuation rate and dose reductions due to ARs¹⁴

Updated analysis with additional 2 years of follow-up (data cutoff April 11, 2022)¹⁵

The safety profile at the updated analysis was consistent with the known safety profile for TAGRISSO

Median time of total treatment exposure was 35.8 months in the adjuvant TAGRISSO arm and 25.1 months in the placebo arm

*NCI CTCAE v4.0.

^†All events were Grade 3.

^‡Includes diarrhea, colitis, enterocolitis, enteritis.

^§Includes aphthous ulcer, cheilitis, gingival ulceration, glossitis, tongue ulceration, stomatitis, and mouth ulceration.

^||Includes abdominal discomfort, abdominal pain, abdominal lower pain, abdominal upper pain, epigastric discomfort, hepatic pain.

^¶Includes rash, rash generalized, rash erythematous, rash macular, rash maculopapular, rash papular, rash pustular, rash pruritic, rash vesicular, rash follicular, erythema, folliculitis, acne, dermatitis, dermatitis acneiform, dermatitis bullous, dermatitis exfoliative generalized, drug eruption, eczema, eczema asteatotic, lichen planus, 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.

**Includes dry skin, skin fissures, xerosis, eczema, xeroderma.

^††Includes pruritus, pruritus generalized, eyelid pruritus.

^‡‡Includes cough, productive cough, upper-airway cough syndrome.

^§§Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain.

^{|| ||}Includes cystitis, urinary tract infection, and urinary tract infection bacterial.

^¶¶Includes asthenia, fatigue.

^##Includes dizziness, vertigo, and vertigo positional.

Adjuvant TAGRISSO: The majority of laboratory abnormalities in ADAURA were Grade 1 or 2¹³*

LABORATORY ABNORMALITIES WORSENING FROM BASELINE IN ≥20% OF PATIENTS IN ADAURA¹³

Laboratory Abnormalities*^†	All grades (%)	Grade 3 or 4 (%)	All grades (%)	Grade 3 or 4 (%)
	TAGRISSO (n=337)		Placebo (n=343)
Hematology
Leukopenia	54	0	25	0
Thrombocytopenia	47	0	7	0.3
Lymphopenia	44	3.4	14	0.9
Anemia	30	0	12	0.3
Neutropenia	26	0.6	10	0.3
Chemistry
Hyperglycemia	25	2.3	30	0.9
Hypermagnesemia	24	1.3	14	1.5
Hyponatremia	20	1.8	16	1.5

The laboratory abnormality in ADAURA that occurred in <20% of patients receiving TAGRISSO was increased blood creatinine (10%).¹³

*NCI CTCAE v4.0.

^†Based on the number of patients with available follow-up laboratory data.

In resectable EGFRm NSCLC, your referral is as mighty as your scalpel

Follow these steps to identify every eligible patient who may benefit from treatment with adjuvant TAGRISSO

Patients presented at multidisciplinary tumor boards are more likely to receive guideline-recommended therapy²¹*

DISCUSS
testing and adjuvant
treatment options with
patients
+
REFER
patients to a medical
oncologist as early as
possible
+
TEST
for EGFR mutations as
soon as possible
=
TREAT
with adjuvant TAGRISSO
for every eligible patient

Ensure institutional protocols are in place to help identify all patients with resectable EGFRm NSCLC

Multidisciplinary team involvement and coordination have been shown to improve patient outcomes in early-stage NSCLC compared to a traditional care model^22†

Pill image is not actual size.

Learn how to test for EGFR mutations

Patients with stage IB should be evaluated for perioperative therapy, including adjuvant treatment.¹⁷
Testing for EGFR mutations in patients with resectable stage IB to IIIA, stage IIIB (T2-T3, N2b; T4, N2) NSCLC is recommended in NCCN Guidelines to inform adjuvant treatment decisions.^17‡§ Osimertinib (TAGRISSO) is the first and only EGFR TKI with an NCCN Category 1 recommendation for adjuvant treatment following surgical resection in patients with EGFRm (exon 19 deletion, L858R mutation) NSCLC and is recommended for a duration of 3 years.^17‡§

^§Osimertinib is recommended following surgical resection in patients with EGFRm (exon 19 deletion, L858R mutation) NSCLC who received previous adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy.¹⁷

*A retrospective cohort analysis that used the Premier inpatient database to identify patients diagnosed with NSCLC who were undergoing treatment in the 77 hospitals within the Ascension Health hospital system during a 5-year period from 2008 to 2012. Patients with stage I-III NSCLC were eligible for inclusion and analysis. The propensity score method was used to populate 2 patient cohorts: those undergoing care coordination through a prospective multidisciplinary care conference (MDC) and those whose care was not coordinated through an MDC. During the 6-year study period, 15,731 patients with NSCLC were identified at 49 hospitals in 26 states that met the entrance criteria for the investigation. 6627 patients met the patient and facility inclusion criteria for the MDC cohort from 27 hospitals. These MDC patients were propensity matched, as previously described, to 6627 patients who met the patient inclusion criteria but whose care was not coordinated through an MDC. In the MDC cohort, 88% of patients (5832/6627) received NCCN-guideline recommended care vs 71% (4705/6627) in the non-MDC cohort (P<0.0001).²¹

^†Bilfinger et al conducted a single-center, retrospective investigation of all lung cancer cases diagnosed between 2002 and 2016 in the Stony Brook University Hospital (SBUH) cancer registry to compare the short-term and long-term survival outcomes of patients with lung cancer treated within the MDT program vs those patients who received a traditional model of cancer care at SBUH. 1956 patients with lung cancer were identified for the MDT group and 2315 patients were identified for the non-MDT group. Short-term and long-term survival rates were both significantly greater among MDT patients vs non-MDT patients at all stages.²²

In resectable NSCLC

A variety of strategies may help improve patient referral from surgeons to oncologists

Help ensure your patient is referred to a medical oncologist for EGFR mutation testing and potential adjuvant treatment

Consider automatic referral to an oncologist for resected patients²³
Ensure timely clinic visit
for follow-up in hospitalized patients²⁴
Discuss surgical cases at your tumor board²⁵
See if surgical databases are available at your institution to use for monitoring referrals²⁵

Check with your multidisciplinary team to ensure any patients with NSCLC who were previously resected have been tested for EGFR mutations and referred to medical oncologists for the chance to receive adjuvant TAGRISSO¹³

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. References: 1. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596-609. 2. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153. 3. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRAS^G12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.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. 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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Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(7):924-937. 35. Socinski MA, Jotte RM, Cappuzzo F, et al; IMpower150 Study Group. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. 36. Nishio M, Barlesi F, West H, et al. Atezolizumab plus chemotherapy for first-line treatment of nonsquamous NSCLC: results from the randomized phase 3 IMpower132 trial. J Thorac Oncol. 2021;16(4):653-664. 37. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med. 2020;383(14):1328-1339. 38. Sezer A, Kilickap S, Gümüş M, et al. 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. References: 1. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596-609. 2. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32(1):147-153. 3. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRAS^G12C somatic mutations across race, sex, and cancer type [correspondence]. N Engl J Med. 2021;384(2):185-187. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non‑Small Cell Lung Cancer V.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. 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. Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non‑small cell lung cancer harboring EGFR mutation. Thorac Cancer. 2020;11(4):1045-1051. 19. Uchida T, Kaira K, Yamaguchi O, et al. Different incidence of interstitial lung disease according to different kinds of EGFR‑tyrosine kinase inhibitors administered immediately before and/or after anti‑PD‑1 antibodies in lung cancer. Thorac Cancer. 2019;10(4):975-979. 20. Kotake M, Murakami H, Naito T, et al. Practical use of osimertinib in Japanese patients with EGFR T790M mutation positive advanced non-small‑cell lung cancer [abstract]. Ann Oncol. 2016;27(suppl9):ix147. 21. Keytruda [package insert]. Rahway, NJ: Merck & Co., Inc; 2025. 22. Tecentriq [package insert]. South San Francisco, CA: Genentech, Inc.; 2025. 23. Opdivo [package insert]. Princeton, NJ: Bristol‑Myers Squibb Company; 2025. 24. Yervoy [package insert]. Princeton, NJ: Bristol‑Myers Squibb Company; 2025. 25. Libtayo [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 2025. 26. Lisberg A, Cummings A, Goldman JW, et al. A phase II study of pembrolizumab in EGFR‑mutant, PD‑L1+, tyrosine kinase inhibitor naïve patients with advanced NSCLC. J Thorac Oncol. 2018;13(8):1138-1145. 27. Reck M, Rodríguez‑Abreu D, Robinson AG, et al; KEYNOTE‑024 Investigators. Pembrolizumab versus chemotherapy for PD‑L1‑positive non‑small‑cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. 28. Mok TSK, Wu YL, Kudaba I, et al; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD‑L1‑expressing, locally advanced or metastatic non‑small‑cell lung cancer (KEYNOTE‑042): a randomised, open‑label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819-1830. 29. Langer CJ, Gadgeel SM, Borghaei H, et al; KEYNOTE‑021 Investigators. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non‑squamous non‑small‑cell lung cancer: a randomised, phase 2 cohort of the open‑label KEYNOTE‑021 study. Lancet Oncol. 2016;17(11):1497-1508. 30. Gandhi L, Rodríguez‑Abreu D, Gadgeel S, et al; KEYNOTE‑189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small‑cell lung cancer. N Engl J Med. 2018;378(22):2078-2092. 31. Carbone DP, Reck M, Paz‑Ares L, et al; CheckMate 026 Investigators. First‑line nivolumab in stage IV or recurrent non‑small‑cell‑lung cancer. N Engl J Med. 2017;376(25):2415-2426. 32. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-2104. 33. Paz‑Ares L, Ciuleanu TE, Cobo M, et al. First‑line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non‑small‑cell lung cancer (CheckMate 9LA): an international, randomised, open‑label, phase 3 trial [published correction appears in Lancet Oncol. 2021;22(3):e92]. Lancet Oncol. 2021;22(2):198-211. 34. West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first‑line treatment for metastatic non‑squamous non‑small‑cell lung cancer (IMpower130): a multicentre, randomised, open‑label, phase 3 trial. Lancet Oncol. 2019;20(7):924-937. 35. Socinski MA, Jotte RM, Cappuzzo F, et al; IMpower150 Study Group. Atezolizumab for first‑line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. 36. Nishio M, Barlesi F, West H, et al. Atezolizumab plus chemotherapy for first‑line treatment of nonsquamous NSCLC: results from the randomized phase 3 IMpower132 trial. J Thorac Oncol. 2021;16(4):653-664. 37. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first‑line treatment of PD‑L1‑selected patients with NSCLC. N Engl J Med. 2020;383(14):1328-1339. 38. Sezer A, Kilickap S, Gümüş M, et al. 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.

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.

Undetectable micrometastases that drive recurrence may remain after complete resection

Despite successful surgery, micrometastases may remain¹

Among patients with resectable NSCLC, adjuvant treatment rates remain low, despite the significant risk of recurrence

Recurrence rates remain high

Among patients with resectable NSCLC, adjuvant treatment rates remain low, despite the significant risk of recurrence

Recurrence rates remain high

Surgical resection or radiation alone may be insufficient⁵

5-YEAR RECURRENCE OR DEATH
RATES IN STAGE IB-III NSCLC^4‡

EGFR mutations occur across stages I-III of NSCLC, driving tumor growth

CNS metastases are a prevalent risk in NSCLC, especially for patients with EGFRm disease^10§

TAGRISSO DATA

reinforce that the unprecedented is possible

Initial DFS analysis: 80% reduced risk of recurrence or death
vs control arm in stage IB-IIIA; HR=0.20 (95% CI: 0.15, 0.27); P<0.0001; N=682. Median DFS was not reached (95% CI: NE, NE) for TAGRISSO and was 27.5 months (95% CI: 22.0, 35.0) for control arm.¹⁴*^†

Target the driver of disease

OS IN RESECTED STAGE IB-IIIA
EGFRm NSCLC^14‡§

Unprecedented improvement in OS in patients with resected stage IB-IIIA EGFRm NSCLC¹³

OS IN RESECTED STAGE IB-IIIA
EGFRm NSCLC^13,15‡§

Adjuvant TAGRISSO: Consistent DFS results across all prespecified patient subgroups

Updated analysis: Consistent DFS results with/without prior adjuvant chemo in resected stage IB-IIIA^14,15§||

OS results across prespecified patient subgroups¹⁸

OVERALL SURVIVAL RESULTS IN PRESPECIFIED PATIENT SUBGROUPS¹⁸

TAGRISSO demonstrated consistent OS results with or without prior adjuvant chemotherapy^15§

Adjuvant TAGRISSO: The majority of adverse reactions in ADAURA were Grade 1 or 2¹³

Adjuvant TAGRISSO: The majority of laboratory abnormalities in ADAURA were Grade 1 or 2¹³*

Follow these steps to identify every eligible patient who may benefit from treatment with adjuvant TAGRISSO

A variety of strategies may help improve patient referral from surgeons to oncologists

IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS

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Undetectable micrometastases that drive recurrence may remain after complete resection

Despite successful surgery, micrometastases may remain1

Among patients with resectable NSCLC, adjuvant treatment rates remain low, despite the significant risk of recurrence

Recurrence rates remain high

Among patients with resectable NSCLC, adjuvant treatment rates remain low, despite the significant risk of recurrence

Recurrence rates remain high

Surgical resection or radiation alone may be insufficient5

5-YEAR RECURRENCE OR DEATH RATES IN STAGE IB-III NSCLC4‡

EGFR mutations occur across stages I-III of NSCLC, driving tumor growth

CNS metastases are a prevalent risk in NSCLC, especially for patients with EGFRm disease10§

TAGRISSO DATA

reinforce that the unprecedented is possible

Initial DFS analysis: 80% reduced risk of recurrence or death vs control arm in stage IB-IIIA; HR=0.20 (95% CI: 0.15, 0.27); P<0.0001; N=682. Median DFS was not reached (95% CI: NE, NE) for TAGRISSO and was 27.5 months (95% CI: 22.0, 35.0) for control arm.14*†

Target the driver of disease

OS IN RESECTED STAGE IB-IIIA EGFRm NSCLC14‡§

Unprecedented improvement in OS in patients with resected stage IB-IIIA EGFRm NSCLC13

OS IN RESECTED STAGE IB-IIIA EGFRm NSCLC13,15‡§

Adjuvant TAGRISSO: Consistent DFS results across all prespecified patient subgroups

Updated analysis: Consistent DFS results with/without prior adjuvant chemo in resected stage IB-IIIA14,15§||

OS results across prespecified patient subgroups18

OVERALL SURVIVAL RESULTS IN PRESPECIFIED PATIENT SUBGROUPS18

TAGRISSO demonstrated consistent OS results with or without prior adjuvant chemotherapy15§

Adjuvant TAGRISSO: The majority of adverse reactions in ADAURA were Grade 1 or 213

Adjuvant TAGRISSO: The majority of laboratory abnormalities in ADAURA were Grade 1 or 213*

Follow these steps to identify every eligible patient who may benefit from treatment with adjuvant TAGRISSO

A variety of strategies may help improve patient referral from surgeons to oncologists

IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

INDICATIONS

Despite successful surgery, micrometastases may remain¹

Surgical resection or radiation alone may be insufficient⁵

5-YEAR RECURRENCE OR DEATH
RATES IN STAGE IB-III NSCLC^4‡

CNS metastases are a prevalent risk in NSCLC, especially for patients with EGFRm disease^10§

Initial DFS analysis: 80% reduced risk of recurrence or death
vs control arm in stage IB-IIIA; HR=0.20 (95% CI: 0.15, 0.27); P<0.0001; N=682. Median DFS was not reached (95% CI: NE, NE) for TAGRISSO and was 27.5 months (95% CI: 22.0, 35.0) for control arm.¹⁴*^†

OS IN RESECTED STAGE IB-IIIA
EGFRm NSCLC^14‡§

Unprecedented improvement in OS in patients with resected stage IB-IIIA EGFRm NSCLC¹³

OS IN RESECTED STAGE IB-IIIA
EGFRm NSCLC^13,15‡§

Updated analysis: Consistent DFS results with/without prior adjuvant chemo in resected stage IB-IIIA^14,15§||

OS results across prespecified patient subgroups¹⁸

OVERALL SURVIVAL RESULTS IN PRESPECIFIED PATIENT SUBGROUPS¹⁸

TAGRISSO demonstrated consistent OS results with or without prior adjuvant chemotherapy^15§

Adjuvant TAGRISSO: The majority of adverse reactions in ADAURA were Grade 1 or 2¹³

Adjuvant TAGRISSO: The majority of laboratory abnormalities in ADAURA were Grade 1 or 2¹³*