Author: Shreeya Nanda
medwireNews: Supplementing first-line abiraterone acetate with olaparib significantly improves the outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC), show phase 3 data reported at the 2022 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA.
The presenting author – Fred Saad, from Centre Hospitalier de l’Université de Montréal in Quebec, Canada – noted that the trial participants were unselected by homologous recombination repair (HRR) mutations, and therefore, these findings demonstrate the clinical benefit of olaparib plus abiraterone irrespective of HRR mutational status.
Fred Saad provides an overview of the PROpel study of olaparib plus abiraterone acetate for the first-line treatment of metastatic castration-resistant prostate cancer, and outlines the next
In the double-blind PROpel trial, 796 men with ongoing androgen deprivation therapy were randomly assigned to receive first-line treatment with either olaparib 300 mg twice a day or matching placebo alongside abiraterone 1000 mg/day plus prednisone or prednisolone 5 mg twice daily.
The addition of olaparib to abiraterone improved the primary endpoint of investigator-assessed radiographic progression-free survival (PFS), at a median of 24.8 months compared with 16.6 months for the control regimen, a statistically and clinically significant difference, said the presenter. This equated to a 34% reduction in the risk for radiographic progression or death with the PARP inhibitor.
The findings were similar when radiographic PFS was assessed by blinded independent central review. Median radiographic PFS was 27.6 months in the olaparib arm and 16.4 months in the placebo arm, giving a significant 39% risk reduction in favor of the olaparib combination.
Furthermore, the radiographic PFS benefit of add-on olaparib was observed both in patients with and without HRR gene mutations (n=226 and 552, respectively), as detected by circulating tumor DNA testing, with significant hazard ratios (HRs) in favor of olaparib of 0.50 and 0.76, respectively.
In the overall study cohort, the addition of olaparib was also associated with significant improvements in the secondary endpoints of time to first subsequent treatment (HR=0.74) and time to second progression or death (HR=0.69).
Overall survival data were not mature at the time of analysis, as just 28.6% of the study population had died, said Saad, but noted that a trend favoring olaparib plus abiraterone was observed (HR=0.86).
He added that the safety and tolerability of the combination “was consistent with the known safety profiles of the individual drugs.”
Adverse events (AEs) of grade 3 or worse occurred in 47.2% of patients in the olaparib group and 38.4% of those in the placebo group, with anemia the most common event of this severity (15.1 vs 3.3%).
The rate of discontinuation of olaparib was higher than that of placebo, at 13.8% versus 7.8%, but a comparable proportion of patients in both groups discontinued abiraterone, at 8.5% and 8.8%, respectively. And the mortality rate due to AEs was also similar, at 4.0% and 4.3%.
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