A phase III trial presented at the ESMO Congress 2019 found that Lynparza® (olaparib) resulted in longer delayed disease progression compared with hormonal agents Xtandi® (enzalutamide) and Zytiga® (abiraterone acetate) in men with metastatic prostate cancer.
The study compared the efficacy of the PARP inhibitor olaparib versus physician’s choice of hormonal therapy (enzalutamide or abiraterone acetate) in two cohorts of men with metastatic castration-resistant prostate cancer. Cohort A included men with alterations in BRCA1, BRCA2, or ATM genes; cohort B included men with alterations in any of 12 other genes known to be involved in DNA repair.
Improved disease progression with olaparib
In Cohort A, median progression-free survival (PFS) was 7.39 months in those receiving olaparib compared with 3.55 months in those receiving hormonal treatment (hazard ratio [HR] = 0.34; P<0.0001). In both cohorts, median PFS was 5.82 months with olaparib versus 3.52 months with hormonal treatment (HR=0.49; P<0.0001).
An interim analysis found that the median overall survival (OS) in Cohort A was 18.5 months with olaparib compared with 15.11 months with hormonal treatment (HR=0.64; P=0.0173). Median OS in both cohorts was 17.51 months with olaparib and 14.26 months with hormonal therapy (HR=0.67; P=0.0063).
Adverse events (AEs) were more common in the olaparib group; however, the median treatment duration was longer with olaparib (7.4 months) than hormone treatment (3.9 months). The most common AEs in the olaparib group were anemia, nausea, decreased appetite, and fatigue. In the olaparib group, 16.4% of patients discontinued treatment due to AEs compared with 8.5% in the hormonal treatment cohort.
“To see such a significant effect on disease progression and other clinically relevant effects such as pain progression and objective response rate is a remarkable achievement in such heavily pre-treated patients with prostate cancer,” said study author Maha Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center, in a press release. “Prostate cancer has lagged behind all other common solid tumors in the use of molecularly targeted treatment, so it is very exciting that now we can personalize an individual’s treatment based on specific genomic alterations in their cancer cells.”
