The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for olaparib in combination with abiraterone and prednisone or prednisolone for the treatment of adults with metastatic castration-resistant prostate cancer (mCRPC).
The sNDA is supported by data from the randomized, double-blind, phase 3 PROpel trial (ClinicalTrials.gov Identifier: NCT03732820) which evaluated the efficacy and safety of olaparib in 796 adults with mCRPC who had not received prior chemotherapy or new hormonal agents (NHAs) in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status. Patients were randomly assigned 1:1 to receive either olaparib 300mg orally twice daily or placebo, in addition to abiraterone and prednisone or prednisolone.
The primary endpoint was radiological progression free survival (rPFS), defined as the time from randomization to radiological progression, as assessed by investigator per RECIST 1.1 and PCWG-3, or death from any cause, whichever occurred first.
According to primary analysis at the first data cutoff, the median rPFS was statistically significantly longer in the olaparib arm compared with the placebo arm, 24.8 vs 16.6 months, respectively (hazard ratio, 0.66; 95% CI, 0.54-0.81; P <.0001) correlating with a 34% risk reduction of disease progression or death. At data cutoff, overall survival data (secondary endpoint) were immature.
The safety and tolerability profile of olaparib and abiraterone was consistent with that observed in previous studies and the known profiles of the individual drugs. The most common adverse reactions were anemia (46%), fatigue (37%) and nausea (28%); adverse events of Grade 3 or worse were anemia (15%), hypertension (4%), urinary tract infection (2%), fatigue (2%), decreased appetite (1%), vomiting (1%), back pain (1%), diarrhea (1%) and nausea (0.3%).
A Prescription Drug User Fee Act target date in the fourth quarter of 2022 has been set for this application.
Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, “There remains a critical unmet need among patients diagnosed with mCRPC, where the prognosis remains poor, and treatment options are limited. Today’s news is another step towards bringing forward a new, much-needed treatment option in this setting. If approved, Lynparza with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease.”
Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is marketed under the trade name Lynparza and is currently approved for the treatment of adults with deleterious or suspected deleterious germline or somatic HRR gene-mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone.
- FDA accepts submission of supplemental New Drug Application for Lynparza® (olaparib) in combination with abiraterone and prednisone or prednisolone for patients with metastatic castration-resistant prostate cancer and grants Priority Review. News release. AstraZeneca and Merck. Accessed August 16, 2022. https://www.businesswire.com/news/home/20220816005290/en/FDA-Accepts-Submission-of-Supplemental-New-Drug-Application-for-LYNPARZA%C2%AE-olaparib-in-Combination-With-Abiraterone-and-Prednisone-or-Prednisolone-for-Patients-With-Metastatic-Castration-Resistant-Prostate-Cancer-and-Grants-Priority-Review
- Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. Published online June 3, 2022. doi:10.1056/EVIDoa2200043
This article originally appeared on MPR