The Food and Drug Administration (FDA) has approved Lynparza® (olaparib) in combination with abiraterone and prednisone or prednisolone for the treatment of adults with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). 

The approval was based on data from the phase 3 PROpel trial ( Identifier: NCT03732820), which included 796 adults with mCRPC who had not received prior chemotherapy or new hormonal agents in the mCRPC setting. 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 Prostate Cancer Working Group (PCWG3) (bone) criteria. The key secondary endpoint was overall survival (OS). Results showed a statistically significant improvement in rPFS with olaparib compared with placebo in the intent-to-treat (ITT) population.

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In an exploratory subgroup analysis of 85 patients with a BRCA gene mutation (BRCAm), olaparib demonstrated clinically meaningful improvements in rPFS (hazard ratio [HR], 0.24; 95% CI, 0.12-0.45) and OS (HR, 0.30; 95% CI, 0.15-0.59) compared with placebo. The median rPFS and median OS were not reached for patients in the olaparib arm compared with a median of 8 months and 23 months, respectively, for the placebo arm.

“Preventing or delaying radiographic progression is an important clinical endpoint in assessing cancer treatment and is very important to patients, their caregivers and their families,” said Andrew Armstrong, MD, ScM, Duke Cancer Institute, Durham, N.C. and an investigator in the trial. “The PROpel results showed the Lynparza combination demonstrated a notable clinically meaningful benefit that should rapidly be considered as the standard of care treatment for patients with BRCAm mCRPC.”

As for safety, the most common adverse reactions reported with olaparib in combination with abiraterone and prednisone or prednisolone were anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia and dizziness (14% each), and abdominal pain (13%).

Lynparza, a poly (ADP-ribose) polymerase (PARP) inhibitor, is also 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.

Additionally, Lynparza is indicated for the treatment of ovarian cancer, breast cancer, and pancreatic cancer.

This article originally appeared on MPR