2018 ASCO: Olaparib in Combination With Abiraterone in Metastatic Castration-Resistant Prostate Cancer
Data presented by Clarke et al at the 2018 ASCO Annual Meeting (Abstract 5003) showed clinical improvement in median radiologic progression-free survival with olaparib (Lynparza) in combination with abiraterone (Yonsa, Zytiga) compared to abiraterone monotherapy, a current standard of care, in metastatic castration-resistant prostate cancer.
The results of Study 08, a randomized, double-blinded, multicenter phase II trial, comparing olaparib in combination with abiraterone (n = 71) to abiraterone monotherapy (n = 71) in patients with previously treated metastatic castration-resistant prostate cancer, regardless of homologous recombination repair mutation status, were selected as a “Best of ASCO” presentation and were published in The Lancet Oncology. The primary endpoint was radiologic progression-free survival. Secondary endpoints included time to second progression or death, overall survival, and health-related quality of life.
Noel Clarke, ChM, Professor of Urological Oncology at the Christie NHS Foundation Trust, Manchester, United Kingdom, said, “This is the first time we have seen an improvement with the use of a PARP inhibitor in combination with abiraterone in patients with metastatic castration-resistant prostate cancer, and this effect may be independent of [homologous recombination repair] status. The data suggest this therapeutic combination may be a promising new treatment approach for this aggressive disease.”
More Findings From Study 08
Median radiologic progression-free survival was 13.8 months with olaparib and abiraterone compared to 8.2 months with abiraterone alone (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.44–0.97; P = .034). Median time to second progression or death was 23.3 months vs 18.5 months (HR = 0.79, 95% CI = 0.51–1.21). Median overall survival was 22.7 months with combination treatment vs 20.9 months with abiraterone alone (HR = 0.91, 95% CI = 0.60–1.38).
Prespecified exploratory subgroup analyses demonstrated an improvement in radiologic progression-free survival, regardless of homologous recombination repair status. Study 08 was not powered for subgroup analyses, time to second progression or death, and overall survival. Homologous recombination repair mutation status was not known for all patients.
The safety of olaparibin combination with abiraterone was also reported, as was the safety of abiraterone monotherapy. Grade ≥ 3 adverse events, serious adverse events and treatment discontinuations due to adverse events were more frequent with combination treatment than abiraterone alone (54% and 28%; 34% and 18%; 30% and 10%, respectively). The most common grade ≥ 3 adverse events in the combination arm were anemia (21%), pneumonia (6%), and myocardial infarction (6%). Serious cardiovascular events occurred in 7 patients in the combination group and 1 patient in the abiraterone group.
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