Multicenter randomized trial of first-line afatinib versus chemotherapy for NSCLC with uncommon EGFR mutations

The randomized ACHILLES/TORG 1834 trial, at 51 centers in Japan, compared afatinib versus platinum-pemetrexed chemotherapy for previously untreated patients with NSCLC with uncommon EGFR alterations (excluding exon 20 insertions and T790M mutations). At the first interim analysis, median progression-free survival was 10.6 months with afatinib versus 5.7 months with chemotherapy (HR 0.421; p=0.0010). The Data and Safety Monitoring Committee recommended early study termination. ORRs were similar across the overall study population and among participants with specific EGFR alterations. The most common grade 3 or higher adverse events with afatinib were diarrhea, paronychia, and ras. The authors conclude that afatinib should be considered the standard initial therapy for patients with NSCLC with sensitizing uncommon EGFR mutations.