Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered A Post Hoc Analysis of the Mainsail Study
Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered A Post Hoc Analysis of the Mainsail Study
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DOI：
10.1001/jamaoncol.2016.3000
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发表时间：
2017-01-01
期刊：
影响因子：
28.4
通讯作者：
de Wit, Ronald
中科院分区：
文献类型：
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作者：
de Morree, Ellen S.;Vogelzang, Nicholas J.;de Wit, Ronald
重要性 转移性去势抵抗性前列腺癌 (mCPRC) 患者的最佳多西紫杉醇周期总数尚未进行研究。目前尚不清楚患者在 6 个周期后继续治疗是否有益。 目的 在 Mainsail 试验的事后分析中，研究给予患者获得临床获益的多西他赛周期数是否是总生存 (OS) 的独立预后因素。 设计、设置和参与者 Mainsail 试验是一项跨国随机 3 期研究，有 1059 名接受多西他赛治疗的 mCRPC 患者参加， 泼尼松和来那度胺 (DPL) 或多西紫杉醇、泼尼松和安慰剂 (DP)。研究患者接受治疗直至疾病进展或出现不可接受的不良反应。与 DP 组相比，DPL 组的中位 OS 较差。由于 DPL 组合的毒性作用增加，与对照组的 8 个周期相比，DPL 患者接受的多西他赛周期较少（中位数为 6 个）。由于两个治疗组的剂量强度相当，我们研究了对 Mainsail 获得临床获益的患者施用的多西紫杉醇周期数是否是 OS 的独立预后因素。我们对意向治疗人群进行了主要的单变量和多变量分析。进行了额外的敏感性分析，排除因疾病进展原因停止治疗的患者以及因其他原因接受 4 个或更少周期多西紫杉醇的患者，最大限度地减少混杂因素的影响。 主要结果和测量 多西紫杉醇周期总数作为 OS 的独立因素。 结果 总体而言，Mainsail 试验的所有 1059 名患者均纳入其中（平均 [SD] 年龄，68.7 [7.89] 年）。 8 个或更多个周期的多西紫杉醇治疗与较高的 OS 相关（风险比 [HR]，1.909；95% CI，1.660-2.194；P
IMPORTANCE The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles.OBJECTIVE To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial.DESIGN, SETTING, AND PARTICIPANTS The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors.MAIN OUTCOMES AND MEASURES Total number of docetaxel cycles delivered as an independent factor for OS.RESULTS Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P