Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration-resistant Prostate Cancer Identifies an Excess of Long-term Survivors.
Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration-resistant Prostate Cancer Identifies an Excess of Long-term Survivors.
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DOI：
10.1016/j.eururo.2020.07.032
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发表时间：
2020-12
期刊：
影响因子：
23.4
通讯作者：
CA184-043, Investigators
中科院分区：
文献类型：
--
作者：
Fizazi K;Drake CG;Beer TM;Kwon ED;Scher HI;Gerritsen WR;Bossi A;den Eertwegh AJMV;Krainer M;Houede N;Santos R;Mahammedi H;Ng S;Danielli R;Franke FA;Sundar S;Agarwal N;Bergman AM;Ciuleanu TE;Korbenfeld E;Sengeløv L;Hansen S;McHenry MB;Chen A;Logothetis C;CA184-043, Investigators
3期试验CA184-043评估了先前接受过多西紫杉醇治疗的转移性阉割抵抗性前列腺癌（mCRPC）患者的骨转移放疗，随后使用Ipilimumab或安慰剂。在先前的分析中，试验的主要终点（总生存期[OS]）没有显著改善。报告OS的最终分析结果。共有799名患者随机接受单剂量放疗，治疗一个或多个骨转移灶，随后接受Ipilimumab （n = 399）或安慰剂（n = 400）。在意向治疗人群中分析OS。基于Kaplan-Meier/Cox方法进行预先指定的探索性子集分析。在初步分析后约2.4年的额外随访期间，721/799例患者死亡。生存分析显示，在7-8个月时曲线出现交叉，随后在该点之后曲线持续分离，这有利于伊匹单抗组。鉴于缺乏比例风险，分段风险模型显示风险比（HR）随时间变化：0-5个月的HR为1.49(95%置信区间1.12,1.99)，5 - 12个月的HR为0.66(0.51,0.86)，12个月以上的HR为0.66（0.52,0.84）。伊匹单抗组的OS率高于安慰剂组，2年（25.2% vs16.6%）， 3年（15.3% vs7.9%）， 4年（10.1% vs3.3%）和5年（7.9% vs 2.7%）。疾病进展是两组患者最常见的死亡原因。ipilimumab组的7名患者（1.8%）和安慰剂组的1名患者（0.3%）的主要死亡原因被报道为研究药物毒性。没有发现长期安全信号。在这项预先计划的长期分析中，对于多西他赛后mCRPC患者，OS更倾向于伊匹单抗加放疗，而不是安慰剂加放疗。伊匹单抗组3、4和5年的OS率大约高出2 - 3倍。经过更长时间的随访，接受伊匹单抗治疗的男性生存率更高，3年及以上的总生存率高出2至3倍。
The phase 3 trial CA184–043 evaluated radiotherapy to bone metastases followed by Ipilimumab or placebo in men with metastatic castrate-resistant prostate cancer (mCRPC) who had received docetaxel previously. In a prior analysis, the trial’s primary endpoint (overall survival [OS]) was not improved significantly. To report the final analysis of OS. A total of 799 patients were randomized to receive a single dose of radiotherapy to one or more bone metastases followed by either Ipilimumab (n = 399) or placebo (n = 400). OS was analyzed in the intention-to-treat population. Prespecified and exploratory subset analyses based on Kaplan-Meier/Cox methodology were performed. During an additional follow-up of approximately 2.4 yr since the primary analysis, 721/799 patients have died. Survival analysis showed crossing of the curves at 7–8 mo, followed by persistent separation of the curves beyond that point, favoring the ipilimumab arm. Given the lack of proportional hazards, a piecewise hazard model showed that the hazard ratio (HR) changed over time: the HR was 1.49 (95% confidence interval 1.12, 1.99) for 0–5 mo, 0.66 (0.51, 0.86) for 5–12 mo, and 0.66 (0.52, 0.84) beyond 12 mo. OS rates were higher in the ipilimumab versus placebo arms at 2 yr (25.2% vs16.6%), 3 yr (15.3% vs7.9%), 4 yr (10.1% vs3.3%), and 5 yr (7.9% vs. 2.7%). Disease progression was the most frequent cause of death in both arms. In seven patients (1.8%) in the ipilimumab arm and one (0.3%) in the placebo arm, the primary cause of death was reported as study drug toxicity. No long-term safety signals were identified. In this preplanned long-term analysis, OS favored ipilimumab plus radiotherapy versus placebo plus radiotherapy for patients with postdocetaxel mCRPC. OS rates at 3, 4, and 5 yr were approximately two to three times higher in the ipilimumab arm. After longer follow-up, survival favored the group of men who received ipilimumab, with overall survival rates being two to three times higher at 3 yr and beyond.
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DOI：
10.1158/1078-0432.ccr-09-0265
发表时间：
2009-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Galloway AE;Kawashima N;Dewyngaert JK;Babb JS;Formenti SC;Demaria S
通讯作者：
Demaria S
影响因子：
10.1
作者：
Kwek, Serena S.;Lewis, Jera;Fong, Lawrence
通讯作者：
Fong, Lawrence
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
10.9
作者：
Cabel L;Loir E;Gravis G;Lavaud P;Massard C;Albiges L;Baciarello G;Loriot Y;Fizazi K
通讯作者：
Fizazi K
影响因子：
11.2
作者：
Oh DY;Cham J;Zhang L;Fong G;Kwek SS;Klinger M;Faham M;Fong L
通讯作者：
Fong L