PROPEL: A randomized phase III trial evaluating the efficacy and safety of olaparib combined with abiraterone as first-line therapy in patients with metastatic castration-resistant prostate cancer (mCRPC)
PROPEL: A randomized phase III trial evaluating the efficacy and safety of olaparib combined with abiraterone as first-line therapy in patients with metastatic castration-resistant prostate cancer (mCRPC)
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PROPEL：一项随机 III 期试验，评估奥拉帕尼联合阿比特龙作为一线治疗转移性去势抵抗性前列腺癌 (mCRPC) 患者的疗效和安全性
DOI：
10.1016/s1569-9056(19)31321-1
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发表时间：
2019
影响因子：
--
通讯作者：
F. Saad
中科院分区：
文献类型：
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作者：
N. Clarke;A. Armstrong;A. Thiery;M. Oya;D. Ye;J. Mateo;C. Goessl;Jinyu Kang;S. Liu;F. Saad
背景：一项II期试验显示，奥拉帕尼（片剂，300 mg bid）联合阿比特龙（1000 mg od +泼尼松/泼尼松5 mg bid）与单独阿比特龙相比，显著延长了先前接受过多西紫杉醇治疗的mCRPC患者（pts）的放射学无进展生存期（rPFS）（中位13.8 vs 8.2个月；风险比0.65,95% CI 0.44-0.97，P=0.034）。无论同源重组修复（HRR）突变状态如何，均可获得治疗效果，这表明两种治疗方法之间的潜在协同作用可能影响更广泛的患者群体。PROpel （EudraCT: 2018-002011-10）是该研究的后续研究，也是首个评估PARP抑制剂联合阿比特龙作为非遗传选择mCRPC患者一线治疗的III期试验。方法：PROpel是一项双盲、安慰剂对照、国际、多中心的随机（1:1）患者研究，在II期试验中，阿比特龙（1000 mg od +强的松/泼尼松5 mg bid） +奥拉帕尼（片剂，300 mg bid）或安慰剂。在mCRPC期，患者必须没有接受过化疗、新的激素药物或其他全身治疗（转移性激素敏感前列腺癌[mHSPC]的多西他赛除外）。随机分组根据转移部位（仅骨、内脏或其他）和mHSPC期多西他赛治疗（是，否）进行分层。主要终点是研究者评估的rPFS （RECIST v1.1[软组织]和前列腺工作癌3组[PCWG-3标准；骨]）。次要目标包括到第一次后续治疗或死亡的时间、到疼痛进展的时间、总生存期和与健康相关的生活质量。安全性和耐受性也将被描述。探索性终点包括HRR亚组分析，以证实疗效与HRR状态无关。正在20个国家的约200个地点进行筛查，以确定约720名患者的目标样本。预计入学将于2018年10月开始。（研究8，NCT01972217）。临床试验信息：NCT03732820。
TPS340Background:A Phase II trial showed olaparib (tablets, 300 mg bid) in combination with abiraterone (1000 mg od plus prednisone/prednisolone 5 mg bid) significantly prolonged radiologic progression-free survival (rPFS) compared with abiraterone alone (median 13.8 vs 8.2 months; hazard ratio 0.65, 95% CI 0.44–0.97,P=0.034) in patients (pts) with mCRPC in the second-line metastatic setting who received prior docetaxel (Clarkeet al. Lancet Oncol2018). Treatment benefits were achieved irrespective of homologous recombination repair (HRR) mutation status, suggesting potential synergy between the two treatments that could impact a broader patient population. PROpel (EudraCT: 2018-002011-10) is the follow-on study to this, and the first Phase III trial to assess a PARP inhibitor in combination with abiraterone as first-line treatment in a genetically unselected mCRPC pt population.Methods:PROpel is a double-blind, placebo-controlled, international, multicenter study of pts randomized (1:1), as for the Phase II trial, to abiraterone (1000 mg od plus prednisone/prednisolone 5 mg bid) plus either olaparib (tablets, 300 mg bid) or placebo. Pts must not have received prior chemotherapy, new hormonal agents or other systemic treatment at mCRPC stage (except docetaxel at metastatic hormone-sensitive prostate cancer stage [mHSPC]). Randomization is stratified according to site of metastases (bone onlyvsvisceralvsother) and docetaxel treatment at mHSPC stage (yes, no). The primary endpoint is investigator-assessed rPFS (RECIST v1.1 [soft tissue] and Prostate Working Cancer Group 3 [PCWG-3 criteria; bone]). Secondary objectives include time to first subsequent therapy or death, time to pain progression, overall survival, and health-related quality of life. Safety and tolerability will also be described. Exploratory endpoints include HRR subgroup analyses to confirm that efficacy is independent of HRR status. Screening across ~200 sites in 20 countries is being conducted to identify a target sample of ~720 pts. Enrollment is expected to begin in October 2018. (Study 8, NCT01972217). Clinical trial information: NCT03732820.