Olaparib, Abiraterone Improves Radiographic Progression-Free Survival in Patients With Metastatic Castration-Resistant Prostate Cancer

New results from the phase 3 PROpel trial of olaparib (Lynparza, Merck) in combination with abiraterone has shown promise in patients with first-line metastatic castration-resistant prostate cancer (mCRPC).

Olaparib is approved for patients with homologous recombination repair (HRR) gene-mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone, according to a press release. PROpel is a randomized, double-blind, phase 3 trial testing the efficacy, safety, and tolerability of olaparib when given with abiraterone and prednisone. The primary endpoint is radiographic progression-free survival (rPFS) and secondary endpoints include overall survival, time to disease progression or death, and time to first subsequent therapy.

According to study results published in NEJM Evidence, the combination plus prednisone significantly improved rPFS in patients with mCRPC with or without HRR gene mutations. The combination was compared with abiraterone plus prednisone, which is the standard of care.

Prostate cancer is the second most common cancer in the world among patients assigned male at birth, with an estimated 1.4 million cases diagnosed worldwide in 2020. Between 10% and 20% of patients with advanced prostate cancer are estimated to develop CRPC within 5 years, and at least 84% of these patients may develop metastases at the time of CRPC diagnosis.

“It is critically important that we identify new first-line treatment options for patients with mCRPC,” said Noel Clarke, MBBS, FRCS, ChM, a urological surgeon, in a press release. “The data published in NEJM Evidence emphasize the therapeutic potential of combining olaparib with abiraterone and prednisone and demonstrate efficacy in a wider group of patients beyond those with documented DNA repair deficiency.”

At a planned interim analysis in September 2021, an independent Data Monitoring Committee concluded that the PROpel trial met its primary endpoint of rPFS. Previous data from the phase 3 trial found that olaparib in combination with abiraterone and prednisone reduced the risk of disease progression or death by 34%.

According to the study, median rPFS was 24.8 months for olaparib plus abiraterone, compared to 16.6 months in the abiraterone arm. The most common adverse events (AEs) in the treatment arm were anemia (46%), fatigue (37%), and nausea (28%). Grade 3 or higher events 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%). Approximately 14% of patients who received olaparib and abiraterone discontinued treatment due to an AE.

“These data demonstrate that the combination of Lynparza with abiraterone and prednisone afforded patients a median radiographic progression-free survival of over 2 years, regardless of biomarker status,” said Cristian Massacesi, MD, chief medical officer and oncology chief development officer at AstraZeneca, in the press release. “If approved, the combination will offer patients with and without HRR gene mutations a new treatment option.”

REFERENCE

Results From Phase 3 PROpel Trial of Lynparza (olaparib) Plus Abiraterone in First-Line Metastatic Castration-Resistant Prostate Cancer Published in NEJM Evidence. News release. Merck; June 21, 2022. Accessed June 28, 2022. https://www.merck.com/news/results-from-phase-3-propel-trial-of-lynparza-olaparib-plus-abiraterone-in-first-line-metastatic-castration-resistant-prostate-cancer-published-in-nejm-evidence/