Final PROpel data confirm OS advantage with abiraterone plus olaparib

The combination of olaparib plus abiraterone in the first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) appears to show a consistent trend toward overall survival (OS) benefit, according to the results of the final prespecified analysis of the phase III PROpel study presented at ASCO GU 2023.

A 7.4-month absolute difference in the median OS emerged between the olaparib plus abiraterone arm and the placebo plus abiraterone arm (47.9 percent maturity; median, 42.1 vs 34.7 months; hazard ratio [HR], 0.81, 95 percent confidence interval [CI], 0.67–1.00; p=0.0544). [ASCO GU 2023, abstract LBA16]

This OS advantage with add-on olaparib was seen across the subgroups of patients defined by mutation status: homologous recombination repair gene (HRR) mutation arm (median, not reached vs 28.5 months; HR, 0.66, 95 percent CI, 0.45–0.95), non-HRR arm (median, 42.1 vs 38.9 months; HR, 0.89, 95 percent CI, 0.70–1.14), BRCA mutation arm (median, not reached vs 23.0 months; HR, 0.29, 95 percent CI, 0.14–0.56), and non-BRCA mutation arm (median, 39.6 vs 38.0 months; HR, 0.91, 95 percent CI, 0.73–1.13).

Already, PROpel met its primary endpoint of radiographic progression-free survival (rPFS) in the primary analysis, wherein the combination of olaparib plus abiraterone was associated with a 34-percent reduction in the risk of disease progression or death as compared with placebo plus abiraterone (HR, 0.66, 95 percent CI, 0.54–0.81; p<0.0001). OS results also favoured the active combination treatment at the time of the primary rPFS analysis (28.6 percent maturity; HR, 0.86, 95 percent CI, 0.66–1.12) and a subsequent interim analysis (40.1 percent maturity; HR, 0.83, 95 percent CI, 0.66–1.03). [NEJM Evid 2022;doi:10.1056/EVIDoa2200043]

“From the primary rPFS analysis presented at ASCO GU last year to the updated OS data presented today, the data reinforce the therapeutic potential of olaparib plus abiraterone and prednisone for patients with mCRPC in the overall trial population and across subgroups,” said senior investigator Dr Noel Clarke, a urological surgeon and professor of urological oncology at Manchester’s Christie/Salford Royal Hospitals and Manchester University in Manchester, England.

“The median OS of 42 months is the longest median reported to date in a phase III trial [on first-line olaparib plus abiraterone for] mCRPC,” Clarke added.

PROpel included a total of 796 patients with mCRPC who were randomly assigned to receive olaparib (300 mg twice daily; n=399; mean age at baseline 69 years) or placebo (n=397; mean age at baseline 70 years), in combination with abiraterone (1,000 mg once daily) plus prednisone/prednisolone (5 mg  twice daily). Of these, 226 patients had HRR mutation while 85 had BRCA mutation.

The safety and tolerability of olaparib plus abiraterone was in line with that observed in previous clinical trials and the known profiles of the individual drugs. Anaemia was the most common grade 3 adverse event in the olaparib plus abiraterone arm (16.1 percent). No new long-term safety issues were identified at the time of this updated analysis.

“The results of PROpel are important for patients and the oncology community alike, providing support for th[e] combination as a potential and critically needed new treatment option in metastatic castration-resistant prostate cancer,” Clarke said.