| The following article features coverage from the ASCO Genitourinary Cancers Symposium 2022. Click here to read more of Cancer Therapy Advisor’s conference coverage. |
Adding olaparib to first-line treatment with abiraterone improved radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to results from the phase 3 PROpel trial.
This represents the first combination approach to deliver consistent clinical benefits for patients in the first-line mCRPC setting, irrespective of homologous recombination repair (HRR) status, said Fred Saad, MD, of the University of Montreal Hospital Center in Quebec, Canada.
He added that, to his knowledge, the rPFS seen with olaparib is the longest rPFS to date in mCRPC. Dr Saad presented these results at the ASCO Genitourinary Cancers Symposium 2022.
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The PROpel trial (ClinicalTrials.gov Identifier: NCT03732820) enrolled 796 patients with mCRPC. Patients were randomly assigned to receive olaparib plus abiraterone (399 patients) or placebo plus abiraterone (397 patients).
Baseline characteristics were well balanced between the arms. The median age was 69 (range, 43-91) years in the olaparib arm and 70 (range, 46-88) years in the placebo arm. Nearly 30% of patients in each arm had HRR mutations.
By investigator assessment, there was a 34% reduction in the risk of progression or death with olaparib. The median rPFS was 24.8 months with olaparib and 16.6 months with placebo (hazard ratio [HR], 0.66; 95% CI, 0.54-0.81; P <.0001).
By blinded independent review, there was a 39% reduction in the risk of progression or death with olaparib. The median rPFS was 27.6 months with olaparib and 16.4 months with placebo (HR, 0.61; 95% CI, 0.49-0.74; P <.0001).
Predefined subgroup analyses showed improvement in rPFS across all subgroups, including in patients with HRR mutations (HR, 0.50; 95% CI, 0.34-0.73) and without them (HR, 0.76; 95% CI, 0.60-0.97).
In addition, olaparib was associated with a significant delay in time to first subsequent treatment or death (HR, 0.74; 95% CI, 0.61-0.90) and time to second progression or death (HR, 0.69; 95% CI, 0.51-0.94).
The overall survival (OS) data were immature, and the median OS was not reached in either treatment arm. However, there was a trend favoring olaparib (HR, 0.86; 95% CI, 0.66-1.12; P =.29).
The overall safety profile of olaparib plus abiraterone was consistent with the safety profile for the individual drugs, Dr Saad said. Furthermore, there was no detriment to quality of life with the combination, allowing most patients to stay on therapy.
The rate of grade 3 or higher adverse event (AEs) was 47.2% in the olaparib arm and 38.4% in the placebo arm. There were 16 fatal AEs in the olaparib arm and 17 in the placebo arm.
The proportion of patients who discontinued the study drug was 13.8% in the olaparib arm and 7.8% in the placebo arm. There was no significant difference in cardiac failure or thromboembolic events between the arms.
Disclosures: This study was sponsored by AstraZeneca in collaboration with Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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Saad F, Armstrong AJ, Thiery-Vuillemin A, et al. PROpel: Phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Presented at ASCO GU 2022; February 17-19, 2022. Abstract 11.
