treatment options for metastatic castration-resistant pros- tate cancer (mCRPC) and sought to determine the opti- mal olaparib strategy for treating it.4 To do so, the study team conducted a systematic review and network meta-analysis, searching the Cochrane, Embase, PubMed, and Web of Science databases using “mCRPC” and “olaparib” as keywords. The researchers identified nine studies from seven clini- cal trials involving 2,355 patients. “For homologous recom- bination repair-mutated mCRPC, combination therapies did not demonstrate significant benefits compared with olaparib alone,” they wrote. “However, for BRCA-mutated mCRPC, olaparib combined with abiraterone improved PFS (HR = 0.61, 95% CrI = 0.41-0.91) and OS (HR = 0.41, 95% CrI = 0.21-0.80) significantly. These significant advantages of olaparib combined with abiraterone were also observed in patients from different prostate-specific antigen subgroups.” The study suggested that olaparib combined with abi- raterone “offers substantial benefits in BRCA mutated type (BRCAmt) mCRPC patients. For those with BRCA wild type homologous recombination repair-mutated mCRPC, olaparib monotherapy is effective.” Other combinations include: • Akeega (Niraparib + Abiraterone): Approved for metastatic castration-sensitive (mCSPC) and resistant (mCRPC) prostate cancer with BRCA2 mutations, • Rucaparib: Used as a targeted therapy for BRCA- positive patients who have progressed after other treatments, and • Upcoming/Novel PARP Inhibitors: Trials are testing new PARP inhibitors like saruparib (AZD5305) to treat high-risk BRCA-positive patients. A continuing problem, however, is that just more than half, 51.2%, of mCRPC patients with BRCA1/2 alterna- tions ever received a PARP inhibitor in a recent study, while 48.8% did not. The cohort study of 443 patients noted that Medicare insurance beneficiaries had higher odds of receiving a PARP inhibitor. The report in JAMA Network Open suggested that, “despite the availability of biomarker-selected life-prolong- ing therapies, a sizeable number of patients with mCRPC and BRCA1/2 alterations do not receive PARP inhibitors, highlighting the need to improve awareness of the data and access to these agents.”5 1 Crawford TB, Tayeb M, Barrett E, Al-Saleem T, et. Al. Pathogenic germline variants in a racially diverse real-world cohort of prostate cancer patients. medRxiv [Preprint]. 2025 Aug 15:2025.08.13.25333614. doi: 10.1101/2025.08.13.25333614. PMID: 40832411; PMCID: PMC12363747. Cancer Res Commun 2 Montgomery B, Lynch JA, Brown J, Maxwell KN, et. Al. Remote delivery of cancer genetic testing in veterans with metastatic prostate cancer: A Million Veteran Program pilot study. Cancer. 2026 Feb 1;132(3):e70283. doi: 10.1002/cncr.70283. PMID: 41615269; PMCID: PMC12857595. 3 Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, et. Al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evid. 2022 Sep;1(9):EVIDoa2200043. doi: 10.1056/ EVIDoa2200043. Epub 2022 Jun 3. PMID: 38319800. 4 Li Y, Li Z, Lu H, Shi P, Liu Y, Liu L, Chen K. PARP Inhibitor Olaparib and Its Combination Therapy in Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Network Meta-analysis. Eur Urol Open Sci. 2025 Dec 31;84:1-12. doi: 10.1016/j.euros.2025.12.014. PMID: 41550797; PMCID: PMC12804617. 5 Ostrowski M, Jo Y, Hage Chehade C, et al. Receipt of PARP Inhibitors in Patients With Metastatic Prostate Cancer Harboring BRCA1/2 Altera- tions. JAMA Netw Open. 2025;8(10):e2534968. doi:10.1001/jamanet- workopen.2025.34968 Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer 2 0 2 6 C O M P E N D I U M O F F E D E R A L M E D I C I N E 5 5 Source: MAGNITUDE Principal Investigators. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-3351. doi:10.1200/JCO.22.01649
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