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

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

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).

Keywords: Afatinib; Japanese; chemotherapy; epidermal growth factor receptor; non-small cell lung cancer.

© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Figures

Figure 1
Figure 1
PFS for afatinib versus cisplatin/pemetrexed according to independent review. (a) All randomized Japanese patients. (b) Japanese patients with common (Del19/L858R) mutations. (c) Japanese patients with Del19 mutation only. (d) Japanese patients with L858R mutation only. CI, confidence interval; HR, hazard ratio; PFS, progression-free survival.
Figure 2
Figure 2
OS for afatinib versus cisplatin/pemetrexed. (a) All randomized Japanese patients. (b) Japanese patients with common (Del19/L858R) mutations. (c) Japanese patients with Del19 mutation only. (d) Japanese patients with L858R mutation only. CI, confidence interval; HR, hazard ratio; OS, overall survival.
Figure 3
Figure 3
Treatment duration and afatinib dosage for Japanese patients in the overall population. Stars represent dose reductions due to diarrhea; circles represent dose reductions due to rash/acne; and triangles represent dose reductions due to rash/acne and diarrhea.

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Source: PubMed

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