title: 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.
abstract: 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).
authors.affiliation: Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Kurashiki Central Hospital, Kurashiki, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: Kyusyu University Hospital, Fukuoka, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.affiliation: Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.affiliation: Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.affiliation: National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.affiliation: Boehringer Ingelheim, Bracknell, UK.
authors.forename: Dan
authors.initials: D
authors.lastname: Massey
authors.affiliation: Nippon Boehringer Ingelheim, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Seki
authors.affiliation: Wakayama Medical University, Wakayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000077716:Afatinib; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000068437:Pemetrexed / Q000008:administration & dosage; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D011799:Quinazolines; D000068437:Pemetrexed; D000077716:Afatinib; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin
keywords: Afatinib; Japanese; chemotherapy; epidermal growth factor receptor; non-small cell lung cancer