Phase II Randomized Study of Figitumumab plus Docetaxel and Docetaxel Alone with Crossover for Metastatic Castration-Resistant Prostate Cancer
Phase II Randomized Study of Figitumumab plus Docetaxel and Docetaxel Alone with Crossover for Metastatic Castration-Resistant Prostate Cancer
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DOI：
10.1158/1078-0432.ccr-13-1869
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发表时间：
2014-04-01
影响因子：
11.5
通讯作者：
Pollak, Michael N.
中科院分区：
文献类型：
--
作者：
de Bono, Johann S.;Piulats, Josep M.;Pollak, Michael N.
目的：Figitumumab 是一种人 IgG(2) 单克隆抗体，靶向胰岛素样生长因子 1 受体 (IGF-1R)，在前列腺癌中具有抗肿瘤活性。这项 II 期试验将患有进展性去势抵抗性前列腺癌的未接受化疗的男性随机化，每 3 周接受 Figitumumab 联合多西他赛/泼尼松（A 组）或多西他赛/泼尼松单独治疗（B1 组）。在 B1 组进展时，患者可以交叉到联合治疗（B2 组）。 实验设计：前列腺特异性抗原 (PSA) 反应是主要终点；对两只手臂的反应评估是非比较性的，并分别进行测试； A 组的 H-0 = 0.45 与 HA = 0.60（α = 0.05；β = 0.09）；对于臂 B2，H-0 = 0.05 与 H-A = 0.20（α = 0.05，β = 0.10）。计划对 A 组和 B1 组的无进展生存期 (PFS) 进行比较。结果：共有 204 名患者被随机分组，其中 199 名患者接受治疗（A 组：97 例；B1 组：102 例）； 37 名患者交叉至 B2 组（开始的中位周期数：A 组 = 8；B1 = 8；B2 = 4）。 A 组和 B1 组中分别有 52% 和 60% 出现 PSA 反应； A 组的主要 PSA 反应目标未达到。中位 PFS 分别为 4.9 个月和 7.9 个月（HR = 1.44；95% 置信区间，1.06-1.96）。 B2 组的 PSA 反应率为 28%。 Figitumumab组合似乎毒性更大，有更多治疗相关的3/4级不良事件（75% vs. 56%），特别是高血糖、腹泻和虚弱，以及治疗相关的严重不良事件（41% vs. 15%），以及全因果关系的5级不良事件（18% vs. 8%）。结论：IGF1R靶向可能值得在特定人群中对该疾病进行进一步评估，但与多西他赛联合治疗则不值得进一步评估。推荐。 (C)2014 AACR。
Purpose: Figitumumab is a human IgG(2) monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF-1R), with antitumor activity in prostate cancer. This phase II trial randomized chemotherapy- naive men with progressing castration-resistant prostate cancer to receive figitumumab every 3 weeks with docetaxel/prednisone (Arm A) or docetaxel/prednisone alone (Arm B1). At progression on Arm B1, patients could cross over to the combination (Arm B2).Experimental Design: Prostate-specific antigen (PSA) response was the primary endpoint; response assessment on the two arms was noncomparative and tested separately; H-0 = 0.45 versus HA = 0.60 (alpha = 0.05; beta = 0.09) for Arm A; H-0 = 0.05 versus H-A = 0.20 (alpha = 0.05, beta = 0.10) for Arm B2. A comparison of progression-free survival (PFS) on Arms A and B1 was planned.Results: A total of 204 patients were randomized and 199 treated (Arm A: 97; Arm B1: 102); 37 patients crossed over to Arm B2 (median number of cycles started: Arm A = 8; B1 = 8; B2 = 4). PSA responses occurred in 52% and 60% of Arms A and B1, respectively; the primary PSA response objective in Arm A was not met. Median PFS was 4.9 and 7.9 months, respectively (HR = 1.44; 95% confidence interval, 1.06-1.96). PSA response rate was 28% in Arm B2. The figitumumab combination appeared more toxic, with more treatmentrelated grade 3/4 adverse events (75% vs. 56%), particularly hyperglycemia, diarrhea, and asthenia, as well as treatmentrelated serious adverse events (41% vs. 15%), and allcausality grade 5 adverse events (18% vs. 8%).Conclusion: IGF1R targeting may merit further evaluation in this disease in selected populations, but combination with docetaxel is not recommended. (C)2014 AACR.