Open AccessAfatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non‐small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX ‐Lung 3
Author(s) -
Kato Terufumi,
Yoshioka Hiroshige,
Okamoto Isamu,
Yokoyama Akira,
Hida Toyoaki,
Seto Takashi,
Kiura Katsuyuki,
Massey Dan,
Seki Yoko,
Yamamoto Nobuyuki
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12723
Subject(s) - pemetrexed , afatinib , medicine , lung cancer , hazard ratio , clinical endpoint , oncology , confidence interval , cisplatin , gastroenterology , chemotherapy , cancer , clinical trial , epidermal growth factor receptor , erlotinib
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 ; NCT 00949650).