Three poly (ADP-ribose) polymerase inhibitor (PARPi) combination regimens have received FDA approval in 2023 for the first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) with deleterious or suspected deleterious BRCA-positive mutations. BRCA mutations make up about 10%–15% of CRPC cases.
Previously, single-agent PARPis were limited only to the second-line setting. These new combination regimens include Merck/AstraZeneca’s Lynparza (olaparib) in combination with abiraterone, Pfizer’s Talzenna (talazoparib) in combination with Pfizer’s Xtandi (enzalutamide), and Janssen’s single-tablet Akeega (niraparib and abiraterone acetate).
Additionally, Pfizer’s Talzenna/Xtandi combination received FDA approval for the first-line treatment of homologous recombination repair (HRR) gene–mutated mCRPC. HRR gene mutations make up about 25% of mCRPC cases.
The attached report examines the differences in approved indication(s), efficacy, costs, and rationale for clinical management of this class, now that all three PARPis have obtained FDA approval for the first-line treatment of mCRPC. The PARPis have other approved indications outside of prostate cancer, including breast, ovarian, and pancreatic cancers; however, this paper focuses on prostate cancer.
It has been recommended that payers implement management strategies for these potentially costly new PARPi combinations that will impact the first-line treatment of prostate cancer.
