Patients with metastatic castration-resistant prostate cancer with or without homologous recombination repair gene mutations may derive benefit from olaparib and abiraterone acetate, according data from the phase 3 PROpel trial.
A first-line combination of olaparib (Lynparza) and abiraterone acetate (Zytiga) yielded a statistically significant improvement in survival compared with abiraterone alone for patients with metastatic castration-resistant prostate cancer (mCRPC) with or without homologous recombination repair (HRR) gene mutations, according to high level findings from the phase 3 PROpel trial (NCT03732820).1
An independent data monitoring committee determined that the study met its primary end point of radiographic progression-free survival among patients who did not receive treatment in the first-line setting, including those who received new hormonal therapies or chemotherapy, according to findings from the planned interim analysis. Additionally, a trend towards improved overall survival (OS) was observed, although the data are currently immature and longer follow up is needed to assess OS as a key secondary end point. Moreover, the combination’s safety profile appears consistent with previous findings.
Data from the study will be presented at an upcoming meeting.
“Today, men with metastatic castration-resistant prostate cancer have limited options in the 1st-line setting, and sadly often the disease progresses after initial treatment with current standards of care. These exciting results demonstrate the potential for Lynparza with abiraterone to become a new 1st-line option for patients regardless of their biomarker status and reach a broad population of patients living with this aggressive disease. We look forward to discussing the results with global health authorities as soon as possible,” Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, said in a press release.
The study enrolled 796 patients with mCRPC who were randomized 1:1 to receive either 300 mg of olaparib twice daily plus 100 mg of abiraterone once daily or twice daily placebo plus the same abiraterone backbone.
“We are encouraged by the PROpel results and the clinical benefit Lynparza in combination with abiraterone demonstrated versus abiraterone alone as a 1st-line treatment option for men with metastatic castration-resistant prostate cancer. Today’s results build on MSD and AstraZeneca’s commitment to bring Lynparza earlier in lines of treatment and to more patients with advanced prostate cancer,” Roy Baynes, senior vice president and head of global clinical development and chief medical officer at MSD Research Laboratories, explained.
Olaparib was previously assessed in a group of patients with previously treated mCRPC who harbor HHR gene mutations as part of the phase 3 PROfound trial (NCT02987543).2 Findings from cohort A the study indicated that single-agent olaparib yielded a median OS benefit of 19.1 months compared with 14.7 months in the control arm (HR, 0.69; 95% CI, 0.50-0.97; P = .02). Moreover, data from cohort B indicated that patients treated with olaparib monotherapy had a median duration of OS of 14.1 months vs 11.5 months in the control group. Investigators concluded that patients with mCRPC who had tumors with at least an alteration in BRCA1/2 or ATM and had experienced progressive disease during prior treatment with a next-generation hormonal therapy derived a significantly longer OS after receiving olaparib compared with agents such as enzalutamide (Xtandi) or abiraterone plus prednisone.