10 reasons to choose

Proven PFS in del19 and L858R based on two large-scale global trials1,2

FOR 1ST-LINE EGFR M+ mNSCLC vs CHEMOTHERAPY

Median progression-free survival (PFS) in LUX-Lung 3

Median PFS for Del 19 Mutations
Median PFS for L858R Mutations

CI=confidence interval; EGFR M+=epidermal growth factor receptor mutation positive; mNSCLC=metastatic non-small cell lung cancer.

*LUX-Lung 3: GILOTRIF 40 mg orally once daily (n=230) vs up to 6 cycles of pemetrexed/cisplatin (n=115) as 1st-line therapy in patients with EGFR M+ mNSCLC; primary endpoint was PFS; key secondary endpoint was OS; LUX-Lung 6: GILOTRIF 40 mg orally once daily (n=242) vs up to 6 cycles of gemcitabine/cisplatin (n=122) as 1st-line therapy in patients with EGFR M+ mNSCLC; primary endpoint was PFS; key secondary endpoint was OS.

Subanalysis of primary endpoint; measured by an independent central radiology review.

Only agent with proven overall survival (OS) in del191,2,3

FOR 1ST-LINE EGFR M+ mNSCLC VS CHEMOTHERAPY

Median OS in LUX-Lung 3

GILOTRIF, Overall Survival in Patients with Del 19 Mutations

An approved treatment option for patients with L858R mutations1,2

  • 27.6 months for afatinib (n=91) vs 40.3 months for pemetrexed-cisplatin (n=47);
    HR 1.30 (95% CI, 0.80-2.11)

HR=hazard ratio.

*In a prespecified subgroup analysis of patients with del19 mutations for the secondary endpoint of OS.

Proven efficacy in even more EGFR mutations1

BASED ON ANALYSIS OF 3 CLINICAL TRIALS*

Based on the responses outlined in the table below

Based on the responses outlined in the table below

  • Among the 75 GILOTRIF-treated patients with uncommon EGFR mutations, 32 patients
    had a non-resistant EGFR mutation
  • The confirmed overall response rate, as assessed by independent radiology review, was
    66% (95% CI, 47%–81%)6
  • At the time of the assessment, among the 21 responders, 52% of patients had a response duration of ≥12 months and 33% had a response duration of ≥18 months1
Activity of GILOTRIF in additional mutations (single or in combination)1*
EGFR mutation Number of patients treated with GILOTRIF (n=32) Number of confirmed responses (n=21) Duration of response, mo (n=21)
S768I 1 1 37.3
S768I and G719X 5 4 4.1, 13.2, 15.2, 29.5
S768I and L858R 2 1 34.5
G719X 8 6 5.7,8.1, 9.6, 23.5,25.2, 31.8
G719X and L861Q 3 2 2.8,6.8
L861Q 12 7 2.8, 4.0, 4.1, 8.3,12.9, 15.2, 20.6
L861Q and del19 1 0 N/A

GILOTRIF may help even more patients in 1st-line EGFR M+ mNSCLC11

*Data from a pooled analysis of LUX-Lung, 2, 3, and 6.

Click here to see clinical trial design information.

Response ongoing at time of censoring.

Established safety profile based on >4200 patients in clinical trials1

ARs reported in LUX-Lung 3 in ≥10% of GILOTRIF-treated patients1

Adverse reaction GILOTRIF (n=229) Grade 3,*% Pemetrexed-cisplatin (n=111) Grade 3,*% GILOTRIF (n=229) All grades,% Pemetrexed-cisplatin (n=111) All grades, %
Gastrointestinal disorders Diarrhea 15 2 96 23
Stomatitis 9 1 71 15
Cheilitis 0 0 12 1
Skin and subcutaneous tissue disorders Rash/acneiform dermatitis 16 0 90 11
Pruritus 0 0 21 1
Dry skin 0 0 31 2
Infections Paronychia§ 11 0 58 0
Cystitis 1 0 13 5
Respiratory, thoracic, and mediastinal disorders Epistaxis 0 1 17 2
Rhinorrhea 0 0 11 6
Investigations Weight decreased 1 1 17 14
General disorders and administration site conditions Pyrexia 0 0 12 6
Eye disorders Conjunctivitis 0 0 11 3

Other clinically important ARs observed in patients treated with GILOTRIF include decreased appetite (29%), nausea (25%), and vomiting (23%)1

AR=adverse reaction.

*None of the ARs in this table except stomatitis (1 patient on GILOTRIF [0.4%]) were grade 4 in severity.

Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.

Includes acne, acne pustular, dermatitis, acneiform dermatitis, dermatosis, drug eruption, erythema, exfoliative rash, folliculitis, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculo-papular, rash pruritic, rash pustular, skin disorder, skin erosion, skin exfoliation, skin fissures, skin lesion, skin reaction, skin toxicity, skin ulcer.

§Includes paronychia, nail infection, nail bed infection.

Serious ARs and discontinuations1

Serious ARs reported in LUX-Lung 31

  • Serious ARs were reported in 29% of patients treated with GILOTRIF. The most frequent serious ARs reported in patients treated with GILOTRIF were diarrhea (6.6%), vomiting (4.8%), and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal ARs in GILOTRIF-treated patients included pulmonary toxicity/ILD-like ARs (1.3%), sepsis (0.43%), and pneumonia (0.43%)

Discontinuations in LUX-Lung 3

  • Discontinuation of therapy in GILOTRIF-treated patients for ARs was 14%1
  • The most frequent ARs that led to discontinuation in GILOTRIF-treated patients were diarrhea (1.3%), ILD (0.9%), and paronychia (0.9%)1

ILD=interstitial lung disease.

Significantly improved survival vs erlotinib1

IN ADVANCED SqCC OF THE LUNG PROGRESSING AFTER CHEMOTHERAPY*

Median Os

Median PFS: 2.4 months with afatinib vs 1.9 months with erlotinib
HR=0.82 (95% CI, 0.68–0.99)1

*In LUX-Lung 8, a head-to-head trial vs erlotinib in patients with metastatic SqCC of the lung with disease progression following ≥4 cycles of platinum-based chemotherapy; primary endpoint was PFS; key secondary endpoint was OS.

Only oral agent approved in SqCC regardless of mutation status1,7

NO BIOMARKER TESTING REQUIRED1,7

LUX-Lung 8: Disease control was improved with afatinib (51%) vs erlotinib (40%)7*

SqCC=squamous cell carcinoma.

*Disease control (complete response, partial response, stable disease, non-complete response, and non-progressive disease) was a secondary endpoint of LUX-Lung 8. Excluding patients with non-complete response and non-progressive disease, disease control with afatinib was 37%, vs 29% with erlotinib, in a post hoc analysis.7

Similar occurrence of serious ARs vs erlotinib1,7

IN ADVANCED SqCC OF THE LUNG (LUX-Lung 8)

SERIOUS ARs REPORTED IN LUX-Lung 81

  • Serious ARs occurred in 44% of patients treated with GILOTRIF. The most frequent serious ARs in patients treated with GILOTRIF were pneumonia (6.6%), diarrhea (4.6%), and dehydration and dyspnea (3.1% each). Fatal ARs in GILOTRIF-treated patients included ILD (0.5%), pneumonia (0.3%), respiratory failure (0.3%), acute renal failure (0.3%), and general physical health deterioration (0.3%).

DISCONTINUATION IN LUX-Lung 8

  • Treatment-related discontinuation due to any ARs was similar in both arms (20% vs 17% for GILOTRIF vs erlotinib)7
  • The most frequent ARs that led to discontinuation in GILOTRIF-treated patients were diarrhea (4.1%) and rash/acne (2.6%)1

ARs REPORTED IN LUX-Lung 8 IN ≥10% OF GILOTRIF-TREATED PATIENTS1

Adverse reaction GILOTRIF (n=392) Grade 3-4, % Erlotinib (n=395) Grade 3-4, % GILOTRIF (n=392) All grades, % Erlotinib (n=395) All grades, %

Gastrointestinal disorders

Diarrhea

Stomatitis*

Nausea

Vomiting

11

4

2

1

3

1

1

1

75

30

21

13

41

11

16

10

Skin and subcutaneous tissue disorders

Rash/acneiform dermatitis

Pruritus

7

0

11

0

70

10

70

13

Infections

Paronychia

1

0

11

5

Metabolism and nutrition disorders

Decreased appetite

3

2

25

26

*Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.

Includes acne, dermatitis, acneiform dermatitis, eczema, erythema, exfoliative rash, folliculitis, rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, rash pustular, skin exfoliation, skin fissures, skin lesion, skin reaction, skin toxicity, skin ulcer.

Includes paronychia, nail infection, nail bed infection.

Dose adjustment reduced the frequency and severity of ARs8

IN A POST HOC ANALYSIS OF LUX-Lung 3

LUX-Lung 3: Over half of patients reduced dose1,5

percentages
  • The most frequent ARs that led to dose reduction in the patients treated with GILOTRIF were diarrhea (20%), rash/acne (19%), stomatitis (10%), and paronychia (14%)1

Among patients that dose reduced in LUX-Lung 3 due to grade 3 ARs1,5

PFS results were consistent among patients with or without
dose adjustments, based on a post hoc analysis of LUX-Lung 38

*Data from intention-to-treat population, which includes both patients with common and uncommon EGFR mutations.

Dose adjustment can be an important strategy to help manage ARs1,3

Initiate therapy at the recommended 40-mg dose
Evaluate patients for ARs within 2 weeks and periodically thereafter
Pause
  • treatment for ≥ grade 3 ARs
  • or ≥ grade 2
    • diarrhea (prolonged)§
    • cutaneous reactions (prolonged or intolerable)ll
    • renal impairment
Resume treatment at 10 mg less per day when AR fully resolves, returns to baseline, or improves to grade 1

In patients with severe renal impairment, the recommended dose of GILOTRIF is 30 mg orally once daily.

National Cancer Institute Common Terminology Criteria for Adverse Events, v3.0.

§Grade ≥2 diarrhea persisting ≥48 hours while taking antidiarrheal medication.

IIGrade 2 cutaneous reactions >7 days.

Permanently discontinue GILOTRIF for1:

Life-threatening bullous, blistering, or exfoliative skin lesions; confirmed ILD;
severe drug‑induced hepatic impairment; persistent ulcerative keratitis; symptomatic left ventricular dysfunction; and severe or intolerable AR occurring at a dose of 20 mg per day.

No known impact of GILOTRIF on CYP450 enzymes or PPIs1,9

DRUG-DRUG INTERACTIONS

  • GILOTRIF is unlikely to affect the metabolism of other drugs that are substrates of CYP450 enzymes1
  • GILOTRIF is unlikely to have an impact on proton pump inhibitors (PPIs)9

EFFECT OF P-GLYCOPROTEIN (P-GP) INHIBITORS AND INDUCERS1

  • P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) can increase exposure to GILOTRIF
  • P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John’s wort) can decrease exposure to GILOTRIF

FOR PATIENTS WHO REQUIRE THERAPY WITH A P-GP INHIBITOR OR INDUCER1

  • P-gp inhibitors
    • Reduce GILOTRIF daily dose by 10 mg if not tolerated. Resume the previous dose after discontinuation of the P-gp inhibitor as tolerated
  • P-gp inducers
    • Increase GILOTRIF daily dose by 10 mg as tolerated. Resume the previous dose 2 to 3 days after discontinuation of the P-gp inducer

CYP450=cytochrome P450.

GILOTRIF: Well established, well studied in over 4200 patients1

LUX-Lung 2: Single-arm, multicenter trial10

  • Single-arm study exploring the anti-tumor efficacy of GILOTRIF in EGFR M+ NSCLC patients with stage IIIB/IV disease
  • Patients were treated with GILOTRIF 50 mg orally once daily (n=99) or 40 mg orally once daily (n=30)
  • Primary endpoint was the proportion of patients with a confirmed objective response, as determined by RECIST 1.0 based on an independent review of imaging

LUX-Lung 3: Global trial in 345 patients with EGFR M+ mNSCLC3

  • Randomized, multicenter, open-label trial that assessed the safety and efficacy of GILOTRIF 40 mg orally once daily (n=230) vs up to 6 cycles of pemetrexed-cisplatin (n=115) as 1st-line therapy in patients with EGFR M+ mNSCLC1
  • Primary endpoint was PFS; key secondary endpoint was OS3
  • Majority of patients had del19 or L858R mutations1,3
    • 49% had del19, 40% had L858R, and 11% had uncommon mutations

LUX-Lung 6: Largest trial in Asian EGFR M+ NSCLC patients11

  • Randomized, multinational, prospective, phase III trial that assessed the safety and efficacy of GILOTRIF 40 mg orally once daily (n=242) vs up to 6 cycles of gemcitabine-cisplatin (n=122) as 1st-line therapy in patients with EGFR M+ mNSCLC
  • Primary endpoint was PFS
  • Majority of patients had del19 or L858R mutations
    • 51% had del19, 38% had L858R, and 11% had uncommon mutations

LUX-Lung 8: Head-to-head vs erlotinib in patients with metastatic SqCC7

  • Randomized, multicenter, open-label phase III trial that assessed the safety and efficacy of GILOTRIF 40 mg orally once daily (n=398) vs erlotinib 150 mg once daily (n=397) in patients with metastatic squamous NSCLC with disease progression following ≥4 cycles of platinum‑based chemotherapy
  • Primary endpoint was PFS; key secondary endpoint was OS

Dosing and administration

Patient selection

  • Select patients for the 1st-line treatment of mNSCLC with GILOTRIF based on the presence of non-resistant EGFR mutations in tumor specimens
  • Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at:
    http://www.fda.gov/CompanionDiagnostics

Advise your patients on GILOTRIF dosing1

  • The recommended dose is 40 mg orally once daily
  • In patients with severe renal impairment (estimated glomerular filtration rate 15 to 29 mL/min/1.73m2), the recommended dose of GILOTRIF is 30 mg orally once daily

Advise your patients on how GILOTRIF should be taken1

  • At least 1 hour before or 2 hours after a meal
  • Not to take a missed dose within 12 hours of the next dose

Treatment duration1

  • Treatment should be continued until disease progression or until no longer tolerated by the patient

Multiple strengths1

  • Multiple tablet strengths available to assist your patients with dose adjustment
gilotrif tablet strengths Back to top of page

IMPORTANT SAFETY INFORMATION AND INDICATIONS AND USAGE
FOR GILOTRIF® (afatinib) TABLETS
WARNINGS AND PRECAUTIONS

IMPORTANT SAFETY INFORMATION
FOR GILOTRIF® (afatinib) TABLETS
WARNINGS AND PRECAUTIONS

Diarrhea
  • GILOTRIF can cause diarrhea which may be severe and can result in dehydration with or without renal impairment. In clinical studies, some of these cases were fatal.
  • For patients who develop Grade 2 diarrhea lasting more than 48 hours or Grade 3 or greater diarrhea, withhold GILOTRIF until diarrhea resolves to Grade 1 or less, and then resume at a reduced dose.
  • Provide patients with an anti‑diarrheal agent (e.g., loperamide) for self‑administration at the onset of diarrhea and instruct patients to continue anti‑diarrheal until loose stools cease for 12 hours.
Bullous and Exfoliative Skin Disorders
  • GILOTRIF can result in cutaneous reactions consisting of rash, erythema, and acneiform rash. In addition, palmar-plantar erythrodysesthesia syndrome was observed in clinical trials in patients taking GILOTRIF.
  • Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating lesions. For patients who develop Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable Grade 2, or Grade 3 cutaneous reactions, withhold GILOTRIF. When the adverse reaction resolves to Grade 1 or less, resume GILOTRIF with appropriate dose reduction.
  • Postmarketing cases of toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) have been reported in patients receiving GILOTRIF. Discontinue GILOTRIF if TEN or SJS is suspected.
Interstitial Lung Disease
  • Interstitial Lung Disease (ILD) or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress syndrome, or alveolitis allergic) occurred in patients receiving GILOTRIF in clinical trials. In some cases, ILD was fatal. The incidence of ILD appeared to be higher in Asian patients as compared to white patients.
  • Withhold GILOTRIF during evaluation of patients with suspected ILD, and discontinue GILOTRIF in patients with confirmed ILD.
Hepatic Toxicity
  • Hepatic toxicity as evidenced by liver function tests abnormalities has been observed in patients taking GILOTRIF. In 4257 patients who received GILOTRIF across clinical trials, 9.7% had liver test abnormalities, of which 0.2% were fatal.
  • Obtain periodic liver testing in patients during treatment with GILOTRIF. Withhold GILOTRIF in patients who develop worsening of liver function. Treatment should be discontinued in patients who develop severe hepatic impairment while taking GILOTRIF.
Keratitis
  • Keratitis has been reported in patients taking GILOTRIF.
  • Withhold GILOTRIF during evaluation of patients with suspected keratitis. If diagnosis of ulcerative keratitis is confirmed, treatment with GILOTRIF should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered. GILOTRIF should be used with caution in patients with a history of keratitis, ulcerative keratitis, or severe dry eye. Contact lens use is also a risk factor for keratitis and ulceration.
Embryo-Fetal Toxicity
  • GILOTRIF can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
  • Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 weeks after the last dose of GILOTRIF. Advise female patients to contact their healthcare provider with a known or suspected pregnancy.

ADVERSE REACTIONS

Adverse Reactions observed in clinical trials were as follows:
First-line treatment of EGFR mutation-positive, metastatic NSCLC
  • In GILOTRIF-treated patients (n=229) the most common adverse reactions (≥20% all grades & vs pemetrexed/cisplatin-treated patients (n=111)) were diarrhea (96% vs 23%), rash/acneiform dermatitis (90% vs 11%), stomatitis (71% vs 15%), paronychia (58% vs 0%), dry skin (31% vs 2%) and pruritus (21% vs 1%). Other clinically important adverse reactions observed in patients treated with GILOTRIF include: decreased appetite (29%), nausea (25%), and vomiting (23%).
  • Serious adverse reactions were reported in 29% of patients treated with GILOTRIF. The most frequent serious adverse reactions reported in patients treated with GILOTRIF were diarrhea (6.6%), vomiting (4.8%), and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse reactions in GILOTRIF-treated patients included pulmonary toxicity/ILD-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%).
  • More GILOTRIF-treated patients (2.2%) experienced ventricular dysfunction (defined as diastolic dysfunction, left ventricular dysfunction, or ventricular dilation; all < Grade 3) compared to chemotherapy‑treated patients (0.9%).
Previously Treated Metastatic Squamous NSCLC
  • In GILOTRIF-treated patients (n=392) the most common adverse reactions (≥20% all grades & vs erlotinib-treated patients (n=395)) were diarrhea (75% vs 41%), rash/acneiform dermatitis (70% vs 70%), stomatitis (30% vs 11%), decreased appetite (25% vs 26%), nausea (21% vs 16%).
  • Serious adverse reactions were reported in 44% of patients treated with GILOTRIF. The most frequent serious adverse reactions reported in patients treated with GILOTRIF were pneumonia (6.6%), diarrhea (4.6%), and dehydration and dyspnea (3.1% each). Fatal adverse reactions in GILOTRIF-treated patients included ILD (0.5%), pneumonia (0.3%), respiratory failure (0.3%), acute renal failure (0.3%), and general physical health deterioration (0.3%).

DRUG INTERACTIONS

Effect of P‑glycoprotein (P‑gp) Inhibitors and Inducers
  • Concomitant use of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib.
  • Concomitant use of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John’s wort) with GILOTRIF can decrease exposure to afatinib.

USE IN SPECIFIC POPULATIONS

Lactation
  • Because of the potential for serious adverse reactions in nursing infants from GILOTRIF, lactating women should not breastfeed during treatment with GILOTRIF and for 2 weeks after the final dose.
Females and Males of Reproductive Potential
  • GILOTRIF may reduce fertility in females and males of reproductive potential. It is not known if the effects on fertility are reversible.
Renal Impairment
  • Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m2) have a higher exposure to afatinib than patients with normal renal function. Administer GILOTRIF at a starting dose of 30 mg once daily in patients with severe renal impairment. GILOTRIF has not been studied in patients with eGFR <15 mL/min/1.73 m2 or who are on dialysis.
Hepatic Impairment
  • GILOTRIF has not been studied in patients with severe (Child Pugh C) hepatic impairment. Closely monitor patients with severe hepatic impairment and adjust GILOTRIF dose if not tolerated.

INDICATIONS AND USAGE

  • GILOTRIF is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test. Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have resistant EGFR mutations.
  • GILOTRIF is indicated for the treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.

GF PROF ISI 01.12.18

Please see the Full Prescribing Information, including Patient Information.

References: 1. GILOTRIF [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. Yang JCH, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151. 3. Lee CK, Wu YL, Ding PN, et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol. 2015;33(17):1958-1965. 4. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327‑3334. 5. Data on file. Boehringer Ingelheim. CTR. 6. Data on file. 7. Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015;16:897-907. 8. Yang JCH, Sequist LV, Zhou C, et al. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials [published online September 6, 2016]. Ann Oncol. 2016. doi:10.1093/annonc/mdw322 9. Peters S, Zimmermann S, Adjei AA. Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: comparative pharmacokinetics and drug-drug interactions. Cancer Treat Rev. 2014;40(8):917-926. 10. Yang JCH, Wu JYS, Hsia TC, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012;13:539-548. 11. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(2):213-222.

References: 1. GILOTRIF [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. Yang JCH, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151. 3. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327‍‑3334. 4. Data on file. Boehringer Ingelheim. CTR. 5. Ke EE, Zhou Q, Zhang QY, et al. A higher proportion of the EGFR T790M mutation may contribute to the better survival of patients with exon 19 deletions compared with those with L858R. J Thorac Oncol. 2017;12(9):1368-1375. 6. Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015;16:897-907.

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