AFATINIB IN EGFR+ NSCLC

Lancet Oncol. 2014 Jan 14. pii: S1470-2045(13)70604-1. doi: 10.1016/S1470-2045(13)70604-1. [Epub ahead of print]

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.

Wu YL1, Zhou C2, Hu CP3, Feng J4, Lu S5, Huang Y6, Li W7, Hou M8, Shi JH9, Lee KY10, Xu CR11, Massey D12, Kim M13, Shi Y14, Geater SL15.

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Abstract

BACKGROUND:

Afatinib-an oral irreversible ErbB family blocker-improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin-a chemotherapy regimen widely used in Asia-for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC.

METHODS:

This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer [American Joint Committee on Cancer version 6], performance status 0-1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m2 on day 1 and day 8 plus cisplatin 75 mg/m2 on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01121393.

FINDINGS:

910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11·0 months, 95% CI 9·7-13·7) than in the gemcitabine and cisplatin group (5·6 months, 5·1-6·7; hazard ratio 0·28, 95% CI 0·20-0·39; p<0 113="" 15="" 239="" 3="" 4="" acne="" adverse="" afatinib="" and="" cisplatin="" common="" compared="" diarrhoea="" events="" gemcitabine="" grade="" group.="" group="" in="" leucopenia="" most="" mucositis="" neutropenia="" nine="" occurred="" of="" or="" p="" patients="" rash="" serious="" stomatitis="" the="" treatment-related="" vomiting="" were="" with="">

INTERPRETATION:

First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population.