Clinical Utility of Olaparib in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review of Current Evidence and Patient Selection.

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive and fatal disease with a median survival of 36 months. With the advent of genetic sequencing to identify individual genomic profiles and acquired tumor-specific pathways, targeted therapies have revolutionized cancer treatment, including the treatment strategy in mCRPC. Poly(adenosine 5'-diphosphate) ribose polymerase inhibitors (PARPi) are oral drugs that target mutations in the homologous recombination repair (HRR) pathway, which are found in approximately 27% of prostate cancer patients. In May 2020, the first PARP inhibitor, olaparib, was approved by the US Food and Drug Administration for men with mCRPC with HHR gene mutations based on the findings of the Phase III PROfound trial that showed improved overall survival in men with mCRPC who received olaparib and whose disease had progressed on a novel hormonal agent. This review summarizes the current evidence and clinical utility of olaparib as treatment in men with mCRPC. We describe the mechanism of action of PARPi, key clinical trials of olaparib in men with mCRPC, and ongoing Phase II and III clinical trials investigating olaparib in combination therapy and as front-line therapy in mCRPC.

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© 2021 LeVee et al.

Déclaration de conflit d'intérêts

Stephen Freedland: Consulting or Advisory Role – Merck, Astellas, AstraZeneca, Pfizer, Janssen, Bayer, Clovis, Sanofi, Myovant, and Exact Sciences. Edwin Posadas: Consulting or Advisory Role – CytoLumina, Genentech/Roche, Janssen Oncology, Janssen Oncology, Novartis; Speakers’ Bureau – Bayer; Research Funding – Pfizer; Patents, Royalties, Other Intellectual Property – Patent on NanoVelcro Assay for CTCs in prostate cancer; Travel, Accommodations, Expenses – TRACON Pharma. Robert Figlin: Leadership – 4Dx, Apollomics; Consulting or Advisory Role – Bristol-Myers Squibb, CBT Pharmaceuticals, Johnson & Johnson; Research Funding – Bristol-Myers Squibb (Inst), Calithera Biosciences (Inst), Exelixis (Inst), Merck (Inst), Peloton Therapeutics (Inst). Dan Theodorescu: Consulting or Advisory Role – Aurora Oncology, Machavert Pharmaceuticals, Merck, Urogen Pharma. Jun Gong: Consultant or Advisory Role – EMD Serono, Elsevier, Exelixis, QED Therapeutics, Natera, Basilea, HalioDx, Eisai, Janssen, Astellas and Amgen. The authors report no other conflicts of interest in this work.