PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials have shown the potential of combining PARPi with other anticancer agents. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of PARPi in patients with metastatic prostate cancer.
MEDLINE, Cochrane CENTRAL, EMBASE, CINAHL, and Web of Science were searched on March 22nd, 2023, for phase 2 or 3 clinical trials. Efficacy (progression-free survival [PFS], overall survival [OS], PSA decline >50% [PSA50], and objective response rate [ORR]) and safety outcomes were assessed in the included studies.
Seventeen clinical trials (PARPi monotherapy [n = 7], PARPi + androgen-receptor signaling inhibitors [ARSI] [n = 6], and PARPi + immune checkpoint inhibitors [ICI] [n = 4]) were included in the quantitative analyses. PARPi monotherapy improved radiographic PFS and OS over SoC in mCRPC patients with alterations in BRCA1 or BRCA2 genes but not in those with alterations in the ATM gene. Higher rates of PSA50 and ORR were reported in participants treated with PARPi + ARSI than in single-agent PARPi or PARPi + ICI. Although the rate of high-grade adverse events was similar across all groups, treatment discontinuation was higher in patients treated with PARPi-based combinations than PARPi monotherapy.
The efficacy of PARPi is not uniform across mCRPC patients with alterations in DNA damage repair genes, and optimal patient selection remains a clinical challenge. No unexpected safety signals for this class of agents emerged from this analysis.
Cancer treatment reviews. 2023 Sep 09 [Epub ahead of print]
Giovanni Maria Iannantuono, Elias Chandran, Charalampos S Floudas, Hyoyoung Choo-Wosoba, Gisela Butera, Mario Roselli, James L Gulley, Fatima Karzai
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States; Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Division of Library Services, Office of Research Services, National Institutes of Health, Bethesda, MD, United States., Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States. Electronic address: .