A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy
A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy
复制标题
DOI：
10.1016/j.lungcan.2016.07.019
复制
发表时间：
2016-09-01
期刊：
影响因子：
5.3
通讯作者：
Nakagawa, Kazuhiko
中科院分区：
文献类型：
--
作者：
Yoh, Kiyotaka;Hosomi, Yukio;Nakagawa, Kazuhiko
目的：雷莫芦单抗加多西紫杉醇可延长铂类治疗后疾病进展的非小细胞肺癌 (NSCLC) 患者的生存期。这项 II 期、双盲、随机、安慰剂对照研究评估了二线雷莫芦单抗-多西他赛在日本 NSCLC 患者中的疗效和安全性。材料和方法：铂类治疗后进展的 NSCLC 患者（28 个日本中心；2012 年 12 月 19 日至 2015 年 5 月 22 日）被随机（计算机生成的序列）接受雷莫芦单抗 10 mg/kg 或安慰剂治疗，随后接受安慰剂多西他赛 60 mg/m(2)（第 1 天，21 天周期）。既往表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂 (TKI) 单药治疗在主要人群中被禁止，但接受 EGFR-TKI 治疗的 EGFR 突变阳性 NSCLC 患者被纳入单独的探索人群。主要终点是无进展生存期（PFS）；次要结局包括总生存率、肿瘤反应率和安全性。研究人员肿瘤评估用于疗效终点。 结果：在主要人群（N = 160 例随机，n = 157 例接受治疗）中，雷莫芦单抗-多西他赛组的中位无进展生存期 (95% CI) 更长（5.22 [3.52-6.97] 个月；n = 76），比安慰剂多西他赛组更长（4.21 [2.83-5.62] 个月；n = 81）；风险比 0.83 (95% CI 0.59-1.16)。雷莫芦单抗-多西他赛组的中位总生存期 (95% CI) 为 15.15 (12.45-26.55) 个月，安慰剂-多西他赛组的中位生存期为 14.65 (11.93-24.44) 个月（风险比 [95% CI] 0.86 [0.56-1.32]）。雷莫芦单抗-多西他赛组的客观缓解率（28.9% vs 18.5%）和疾病控制率（78.9% vs 70.4%）在数值上高于安慰剂-多西他赛组。大多数不良事件的发生率和严重程度相似，但雷莫芦单抗-多西他赛组中发热性中性粒细胞减少症 (34.2%) 比安慰剂-多西他赛组 (19.8%) 更常见。结论：二线雷莫芦单抗-多西他赛改善的 PFS 与 REVEL 试验中观察到的结果相似，在日本 NSCLC 患者中具有可控的安全性。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
Objectives: Ramucirumab plus docetaxel prolongs survival in patients with non-small cell lung cancer (NSCLC) with disease progression after platinum-based therapy. This phase II, double-blind, randomized, placebo-controlled study assessed efficacy and safety of second-line ramucirumab-docetaxel in Japanese patients with NSCLC.Materials and methods: Patients with NSCLC with progression after platinum-based therapy (28 Japanese sites; 19 December, 2012 to 22 May, 2015) were randomized (computer-generated sequence) to ramucirumab 10 mg/kg or placebo, followed by docetaxel 60 mg/m(2) (Day 1, 21-day cycle). Prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) monotherapy was prohibited in the primary population, but EGFR mutation-positive NSCLC patients who were treated with EGFR-TKI were enrolled as a separate exploratory population. Primary endpoint was progression-free survival (PFS); secondary outcomes included overall survival, tumor response rates, and safety. Investigator tumor assessments were used for the efficacy endpoints.Results: In the primary population (N = 160 randomized, n=157 treated), median (95% CI) PFS was longer with ramucirumab-docetaxel (5.22 [3.52-6.97] months; n=76) than with placebodocetaxel (4.21 [2.83-5.62] months; n = 81); hazard ratio 0.83 (95% CI 0.59-1.16). Median (95% CI) overall survival was 15.15 (12.45-26.55) months with ramucirumab-docetaxel and 14.65 con (11.93-24.44) months with placebo-docetaxel (hazard ratio [95% CI] 0.86 [0.56-1.32]). Objective response rate (28.9% vs 18.5%) and disease control rate (78.9% vs 70.4%) were numerically greater with ramucirumab-docetaxel than with placebo-docetaxel. Incidence and severity of most adverse events were similar, but febrile neutropenia was more common with ramucirumab-docetaxel (34.2%) than with placebo-docetaxel (19.8%).Conclusion: Second-line ramucirumab-docetaxel improved PFS similar to that seen in the REVEL trial with a manageable safety profile in Japanese patients with NSCLC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.