LUX-Lung 7 compared afatinib (40 mg daily) with gefitinib (250 mg daily) in treatment-naïve patients with stage IIIb/IV non–small-cell lung cancer (NSCLC) who harbor a common EGFR mutation (Del19/L858R). Coprimary end points were progression-free survival (PFS) by independent review, time-to-treatment failure (TTF), and overall survival (OS).
A total of 319 patients were randomized in the LUX-Lung 7 trial: 160 to afatinib and 159 to gefitinib. At the time of primary analysis, PFS (P=0.017), TTF (P=0.007), and overall response rate (ORR; 70% vs 56%; P=0.008) were significantly improved with afatinib versus gefitinib.
After updated analysis, PFS and TTF results were similar to the initial findings: the hazard ratio (HR) for PFS was 0.74; HR for TTF was 0.75. Despite the significant HR, median PFS was essentially the same: 11.0 months for afatinib and 10.9 months for gefitinib. Median TTF results were 13.7 months and 11.5 months for afatinib and gefitinib, respectively.
The data cut-off for OS analysis occurred in April 2016 when median follow-up was 42.6 months. At this time point, a minority of patients in each arm had received treatment for more than 24 months: 25% (afatinib) and 13% (gefitinib). Most patients went on to receive 1 or more subsequent systemic anticancer treatments. Approximately half of these patients received a subsequent EGFR tyrosine kinase inhibitor, including investigational third-generation agents, osimertinib (14%) and olmutinib (14%).
The OS difference for patients receiving afatinib was not significantly different compared with patients receiving gefitinib. Median OS for afatinib was 27.9 months versus 24.5 months for gefitinib, a 3.4-month difference (HR, 0.86; 95% confidence interval, 0.66-1.12).
The most common grade ≥3 adverse events (AEs) were diarrhea (13%) and rash/acne (9%) with afatinib, and elevated ALT/AST (9%) with gefitinib versus 2% for gefitinib. However, the treatment discontinuation rate due to drug-related AEs was the same (6%) in both arms.
Researchers concluded that afatinib offers significant clinical benefits, including improved PFS, TTF, and ORR compared with gefitinib in EGFR-mutated NSCLC patients, as well as a manageable AE profile. Use of afatinib did not significantly improve OS relative to gefitinib.
Park K, et al. WCLC 2016. Abstract OA 23 05. ID 5347.