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Overall survival (OS) in patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring common (Del19/L858R) epidermal growth factor receptor mutations (EGFR mut): Pooled analysis of two large open-label phase III studies (LUX-Lung 3 [LL3] and LUX-Lung 6 [LL6]) comparing afatinib with chemotherapy (CT).
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Background: Afatinib (A) is an oral, irreversible ErbB family blocker of EGFR, HER2, ErbB3 and ErbB4 signalling. LL3 compared A with cisplatin/pemetrexed in 345 pts recruited globally and LL6 compared A with gemcitabine/cisplatin in 364 Asian pts. The primary analysis (2012) showed improved progression-free survival (PFS) with A versus CT in the overall EGFR mut positive population (HR=0.58 [LL3], HR=0.28 [LL6]) and pts with common (Del19/L858R) EGFR mut (HR=0.47 [LL3], HR=0.25 [LL6]). The FDA has approved A for the first-line treatment of pts with advanced NSCLC harboring common EGFR mut. Here we present a pooled analysis of mature OS data among such pts. Methods: Treatment-naïve pts with EGFR mut stage IIIB/IV NSCLC were randomized 2:1 to 40 mg A or up to 6 cycles of standard CT and stratified by EGFR mut and race (LL3). The primary endpoint was PFS, with OS as a key secondary endpoint. Adverse events were also recorded. Results: The pooled analysis included 631/709 pts randomized into LL3 and LL6 with common EGFR mut (Del19=355, L858R=276); 419 pts received A and 212 received CT. At the time of analysis (January 2014), 404 (64%) pts had died. Median follow-up for OS was 36.5 months. Following progression, 78% of pts received subsequent systemic therapies (median of 3 regimens); 68% in the CT group received EGFR TKIs and 70% in the A group received CT. OS was significantly improved with A versus CT (median 27.3 vs 24.3 months, HR=0.81 [CI 0.66, 0.99; p=0.037]). Individual HRs for OS in LL3 and LL6 were consistent with the pooled analysis. Among Del19 pts the HR=0.59 (CI 0.45, 0.77; p<0.001) and in L858R pts the HR=1.25 (CI 0.92, 1.71; p=0.160). Updated PFS and safety findings were consistent with earlier primary reports. Conclusions: This pooled analysis reveals that first-line A significantly improves OS in pts with advanced NSCLC harboring common EGFR mut (Del19/L858R) compared with CT. This is the first analysis to show that genotype-directed therapy for EGFR mut pts can improve survival. Clinical trial information: NCT00949650.
Abstracts by James Chih-Hsin Yang:
A phase I dose-defining study for MK-2206 combined with gefitinib in NSCLC population enriched with EGFR mutation.Meeting: 2014 ASCO Annual Meeting | Abstract No: e19013
Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients (pts) with EGFR inhibitor–resistant non-small cell lung cancer (NSCLC).Meeting: 2014 ASCO Annual Meeting | Abstract No: 8009^