三期、随机、安慰剂对照、双盲试验莫特沙尼（AMG-706）联合紫杉醇和卡铂治疗东亚晚期非鳞状非小细胞肺癌患者。
Phase III, Randomized, Placebo-Controlled, Double-Blind Trial of Motesanib (AMG-706) in Combination With Paclitaxel and Carboplatin in East Asian Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer.
机构信息
Kaoru Kubota, Nippon Medical School; Kaori Hara and Takayuki Asato, Takeda Pharmaceutical, Tokyo; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Fumihiro Oshita, Kanagawa Prefectural Ashigarakami Hospital, Matsuda; Toyoaki Hida, Aichi Cancer Center Hospital, Nagoya; Kiyotaka Yoh, National Cancer Center Hospital East, Chiba; Hidetoshi Hayashi, Hiroyasu Kaneda, and Kazuhiko Nakagawa, Kindai University Faculty of Medicine; Hidetoshi Hayashi, Kishiwada Municipal Hospital, Osaka; Terufumi Kato, Kanagawa Cardiovascular and Respiratory Center, Yokohama; Kazuhiko Yamada, Kurume University School of Medicine; Yukito Ichinose, National Kyushu Cancer Center, Fukuoka; Hiroshi Tanaka, Niigata Cancer Center Hospital, Niigata, Japan; Keunchil Park, Samsung Biomedical Research Institute, Seoul; Eun Kyung Cho, Gachon University; Kyung-Hee Lee, Inha University Hospital, Incheon, South Korea; Chih-Bin Lin, Buddhist Tzu-Chi General Hospital, Hualien; James Chih-Hsin Yang, National Taiwan University Hospital; National Taiwan University Cancer Center, Taipei City, Peoples Republic of China.
出版信息
J Clin Oncol. 2017 Nov 10;35(32):3662-3670. doi: 10.1200/JCO.2017.72.7297. Epub 2017 Sep 13.
Purpose This phase III, randomized, placebo-controlled, double-blind study determined whether motesanib improved progression-free survival (PFS) compared with placebo in combination with paclitaxel and carboplatin (P/C) in East Asian patients with stage IV/recurrent nonsquamous non-small-cell lung cancer. Patients and Methods Patients were randomly assigned (1:1) to receive oral motesanib 125 mg or placebo once daily plus paclitaxel 200 mg/m IV and carboplatin area under the concentration-time curve 6 mg/mL ⋅ min IV for up to six 3-week cycles. Random assignment was stratified by epidermal growth factor receptor status, region, and weight loss in the 6 months before assignment. The primary end point was PFS, the key secondary end point was overall survival, and other secondary end points were objective response rate, time to tumor response, duration of response, and adverse events (AEs). Results Four hundred one patients were assigned to receive motesanib plus P/C (n = 197) or placebo plus P/C (n = 204). Median PFS was 6.1 v 5.6 months for motesanib versus placebo (stratified log-rank test P = .0825; stratified hazard ratio, 0.81; 95% CI, 0.64 to 1.03; P = .0820); median overall survival was not reached versus 21.6 months ( P = .5514). In secondary analyses, the objective response rate was 60.1% v 41.6% ( P < .001); median time to tumor response, 1.4 v 1.6 months, and median duration of response, 5.3 v 4.1 months. Incidence of grade ≥ 3 AEs (86.7% v 67.6%) and AEs that led to drug discontinuation (32.7% v 14.2%) were higher with motesanib than with placebo. AEs reported more frequently with motesanib were GI disorders, hypertension, and gallbladder related. Conclusion Motesanib plus P/C did not significantly improve PFS versus placebo plus P/C in East Asian patients with stage IV/recurrent nonsquamous non-small-cell lung cancer.
目的 这项 III 期、随机、安慰剂对照、双盲研究旨在确定与安慰剂相比，莫特沙尼联合紫杉醇和卡铂（P/C）治疗东亚 IV 期/复发性非鳞状非小细胞肺癌患者是否能改善无进展生存期（PFS）。
方法 患者按 1:1 随机分配接受口服莫特沙尼 125mg 或安慰剂，每日 1 次，联合紫杉醇 200mg/m2 静脉滴注和卡铂 AUC6mg/mL·min 静脉滴注，最多 6 个 3 周周期。随机分组按表皮生长因子受体状态、地区和分组前 6 个月体重减轻进行分层。主要终点为 PFS，关键次要终点为总生存期，其他次要终点为客观缓解率、肿瘤反应时间、缓解持续时间和不良事件（AE）。
结果 401 例患者被分配接受莫特沙尼加 P/C（n=197）或安慰剂加 P/C（n=204）治疗。莫特沙尼组和安慰剂组的中位 PFS 分别为 6.1 个月和 5.6 个月（分层对数秩检验 P=0.0825；分层风险比，0.81；95%CI，0.64 至 1.03；P=0.0820）；中位总生存期未达到 21.6 个月（P=0.5514）。在次要分析中，客观缓解率为 60.1%比 41.6%（P<0.001）；肿瘤反应时间的中位时间为 1.4 个月比 1.6 个月，缓解持续时间的中位时间为 5.3 个月比 4.1 个月。莫特沙尼组的 3 级及以上 AE 发生率（86.7%比 67.6%）和因 AE 停药的发生率（32.7%比 14.2%）均高于安慰剂组。莫特沙尼组报告的更常见的 AE 为胃肠道疾病、高血压和胆囊相关疾病。
结论 与安慰剂加 P/C 相比，莫特沙尼加 P/C 并未显著改善东亚 IV 期/复发性非鳞状非小细胞肺癌患者的 PFS。
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