Journal Article

Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non‐small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX‐Lung 3

Okamoto, Isamu, Yamamoto, Nobuyuki, Kato, Terufumi, Seki, Yoko, Yokoyama, Akira, Kiura, Katsuyuki, Seto, Takashi, Hida, Toyoaki, Massey, Dan, Yoshioka, Hiroshige

2015

Overview

In LUX‐Lung 3, afatinib significantly improved progression‐free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation‐positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX‐Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut‐off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06–0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20–1.25; P = 0.1309). Median OS (data cut‐off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40–1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29–1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13–0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40–3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment‐related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation‐positive lung adenocarcinoma patients and OS in Del19 but not L858R patients (www.clinicaltrials.gov; NCT00949650). In subgroup analyses of LUX‐Lung 3, afatinib significantly improved progression‐free survival versus cisplatin/pemetrexed in Japanese patients with EGFR mutation‐positive lung adenocarcinoma. Overall survival was significantly improved with afatinib in Japanese patients with Del19 mutation, while overall survival in Japanese patients with L858R mutation was similar between treatment arms.

• Publisher: John Wiley & Sons, Inc,John Wiley & Sons, Ltd
• Subject: Acne / Adenocarcinoma / Adenocarcinoma - drug therapy / Adenocarcinoma - genetics / Adenocarcinoma of Lung / Adult / Afatinib / Aged / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Appetite loss / Asian People - genetics / Cancer therapies / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Chemotherapy / Cisplatin / Cisplatin - administration & dosage / Confidence intervals / Diarrhea / Disease control / Disease-Free Survival / Drug dosages / Epidermal growth factor / epidermal growth factor receptor / Epidermal growth factor receptors / ErbB Receptors - genetics / Female / Humans / Japanese / Leukopenia / Lung cancer / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Male / Middle Aged / Mutation / Mutation - genetics / Nausea / Neutropenia / non‐small cell lung cancer / Original / Patients / Pemetrexed - administration & dosage / Pharmaceuticals / Quinazolines - therapeutic use / Research funding / Stomatitis / Studies / Tumors