阿法替尼对比顺铂联合培美曲塞用于携带表皮生长因子受体（EGFR）激活突变的日本晚期非小细胞肺癌患者：LUX-Lung 3研究的亚组分析
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.
作者信息
Kato Terufumi, Yoshioka Hiroshige, Okamoto Isamu, Yokoyama Akira, Hida Toyoaki, Seto Takashi, Kiura Katsuyuki, Massey Dan, Seki Yoko, Yamamoto Nobuyuki
机构信息
Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
Kurashiki Central Hospital, Kurashiki, Japan.
出版信息
Cancer Sci. 2015 Sep;106(9):1202-11. doi: 10.1111/cas.12723. Epub 2015 Jul 25.
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).
在LUX-Lung 3研究中，与顺铂/培美曲塞相比，阿法替尼显著改善了EGFR突变阳性肺腺癌患者的无进展生存期（PFS），并改善了Del19患者的总生存期（OS）。对LUX-Lung 3研究中的日本患者进行了预先计划的分析。患者按2:1随机分组接受阿法替尼或顺铂/培美曲塞治疗，按突变类型（Del19/L858R/其他）进行分层。主要终点为PFS（独立评估）。次要终点包括OS、客观缓解率和安全性。在所有日本患者（N = 83）中，阿法替尼与顺铂/培美曲塞相比的中位PFS（数据截止时间：2012年2月）分别为13.8个月和6.9个月（风险比[HR]，0.38；95%置信区间[CI]，0.20 - 0.70；P = 0.0014），常见突变（Del19/L858R）患者（HR，0.28；95% CI，0.15 - 0.52；P < 0.0001）和Del19突变患者（HR，0.16；95% CI，0.06 - 0.39；P < 0.0001）的改善更为显著。L858R患者的PFS也有所改善（HR，0.50；95% CI，0.20 - 1.25；P = 0.1309）。在所有日本患者中，阿法替尼与顺铂/培美曲塞相比的中位OS（数据截止时间：2013年11月）分别为46.9个月和35.8个月（HR，0.75；95% CI，0.40 - 1.43；P = 0.3791），常见突变患者（HR，0.57；95% CI，0.29 - 1.12；P = 0.0966）和Del19突变患者（HR，0.34；95% CI，0.13 - 0.87；P = 0.0181）获益更大；L858R患者的OS无显著差异（HR，1.13；95% CI，0.40 - 3.21；P = 0.8212）。研究治疗中断后，大多数患者（93.5%）接受了后续抗癌治疗。最常见的治疗相关不良事件是阿法替尼组的腹泻、皮疹/痤疮、指甲病变和口腔炎，以及顺铂/培美曲塞组的恶心、食欲减退、中性粒细胞减少和白细胞减少。在日本EGFR突变阳性肺腺癌患者中，与顺铂/培美曲塞相比，阿法替尼显著改善了PFS，在Del19患者中改善了OS，但在L858R患者中未改善（www.clinicaltrials.gov；NCT00949650）。
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