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Olaparib Combined with Abiraterone versus Olaparib Monotherapy for Patients with Metastatic Castration-resistant Prostate Cancer Progressing after Abiraterone and Harboring DNA Damage Repair Deficiency: A Multicenter Real-world Study

奥拉帕尼 阿比曲酮 医学 前列腺癌 肿瘤科 醋酸阿比特龙酯 内科学 癌症 雄激素剥夺疗法 聚ADP核糖聚合酶 雄激素受体 DNA 遗传学 聚合酶 生物
作者
Jun Xie,Hanxu Guo,Baijun Dong,Wei Chen,Chengqi Jin,Qiufan Xu,Li Ding,Wujianhong Liu,Shengrong Dong,Tingting Zhao,Yang Yu,Changcheng Guo,Xudong Yao,Bo Peng,Bin Yang
出处
期刊:European Urology Oncology [Elsevier BV]
卷期号:7 (5): 1088-1096 被引量:2
标识
DOI:10.1016/j.euo.2024.02.005
摘要

Background and objective Olaparib + abiraterone has a combined antitumor effect in metastatic castration-resistant prostate cancer (mCRPC), but the efficacy of this combination in patients with DNA damage repair (DDR)-deficient mCRPC progressing after abiraterone is unknown. Our aim was to compare the efficacy of olaparib + abiraterone versus olaparib monotherapy for patients with DDR-deficient mCRPC progressing after abiraterone. Methods The study included 86 consecutive patients with DDR-deficient mCRPC progressing after abiraterone: 34 received olaparib + abiraterone, and 52 received olaparib monotherapy. DDR-deficient status was defined as the presence of a DDR gene with a pathogenic or likely pathogenic variant (DDR-PV), or with a variant of unknown significance (DDR-VUS). We assessed progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. Potential factors influencing PFS and OS were compared between the treatment arms using Cox proportional-hazards models. The prostate-specific antigen (PSA) response, the treatment effect across subgroups, and adverse events (AEs) were also evaluated. Key findings and limitations Median follow-up was 9 mo. In the overall cohort, median PFS and OS were significantly longer in the combination arm than in the monotherapy arm (PFS: 6.0 vs 3.0 mo; hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.25–0.67; p < 0.01; OS: 25.0 vs 12.0 mo; HR 0.30, 95% CI 0.14–0.67; p < 0.01). PSA responses were significantly higher following combination therapy versus monotherapy. Combination therapy had significantly better efficacy in the DDR-PV and DDR-VUS subgroups, and was an independent predictor of better PFS and OS. AE rates were acceptable. The retrospective nature, small sample size, and short follow-up are limitations. Conclusions Olaparib + abiraterone resulted in better PFS and OS than olaparib alone for patients with DDR-deficient mCRPC progressing after abiraterone. These results need to be confirmed by a large-scale prospective randomized controlled trial. Patient summary Our study shows that the drug combination of olaparib plus abiraterone improved survival over olaparib alone for patients who have mutations in genes affecting DNA repair and metastatic prostate cancer resistant to hormone therapy. The results provide evidence of a synergistic effect of the two drugs in these patients.
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