Safety and efficacy of first‐line dacomitinib in Japanese patients with advanced non‐small cell lung cancer

In a subgroup of Japanese patients in the ARCHER 1050 randomized phase 3 trial, we evaluated the efficacy and safety and determined the effects of dose modifications on adverse events (AE) and therapy management of first‐line oral dacomitinib 45 mg compared with oral gefitinib 250 mg, each once daily in 28‐d cycles, in patients with EGFR‐activating mutation–positive (EGFR‐positive; exon 19 deletion or exon 21 L858R substitution mutations) advanced non‐small cell lung cancer (NSCLC). The primary endpoint was progression‐free survival (PFS; RECIST, version 1.1, by blinded independent review). In 81 Japanese patients (40 dacomitinib, 41 gefitinib), PFS was longer with dacomitinib compared with gefitinib (hazard ratio [HR], 0.544 [95% confidence interval {CI}, 0.307‐0.961]; 2‐sided P = .0327; median 18.2 for dacomitinib [95% CI, 11.0‐31.3] mo, 9.3 [95% CI, 7.4‐14.7] mo for gefitinib). The most common Grade 3 AEs were dermatitis acneiform with dacomitinib (27.5%) and increased alanine aminotransferase with gefitinib (12.2%). A higher proportion of patients receiving dacomitinib (85.0%) compared with gefitinib (24.4%) had AEs leading to dose reduction. Incidence and severity of diarrhea, dermatitis acneiform, stomatitis and paronychia were generally reduced after dacomitinib dose reductions and dacomitinib treatment duration was generally longer in patients with a dose reduction in comparison with those without a dose reduction. Our results confirmed the efficacy and safety of first‐line dacomitinib in Japanese patients with EGFR‐positive advanced NSCLC. We evaluated the efficacy and safety of first‐line dacomitinib compared with gefitinib in a subgroup of Japanese patients with EGFR‐activating mutation–positive advanced non‐small cell lung cancer who were enrolled in the ARCHER 1050 randomized phase 3 trial. Results for the primary efficacy endpoint in the Japanese patients (n = 81) were consistent with the results in the overall ARCHER 1050 population; there was a clinically meaningful prolongation of median PFS by 8.9 mo favoring dacomitinib. The safety profile of dacomitinib was manageable by dose reduction or temporary dose interruption and no new safety signals were observed in the population of Japanese patients compared with the overall ARCHER 1050 study population.