Abiraterone in Combination with Olaparib Shows Clinical Benefit for mCRPC Patients

Chicago—Results from a previous study of patients with metastatic castration-resistant prostate cancer (mCRPC) demonstrated improved response to the PARP inhibitor olaparib as monotherapy compared with patients without a homologous recombination repair mutation (HRRm) [Mateo j et al., NEJM 2015).

During an oral session at the ASCO 2018 Annual Meeting, Noel Clarke, MD, and colleagues reported data from a phase 2, placebo-controlled trial of olaparib in combination with abiraterone in post-chemotherapy mCRPC patients whose tumors did not need to have a HRRm. The session was titled Olaparib Combined with Abiraterone in Patients (pts) with Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Randomized Phase II Trial.

The study cohort included 142 patients who were randomized in a 1:1 ratio to receive 300 mg tablets twice a day post-docetaxel (tablets; combination) or placebo (comparator) plus abiraterone (1000 mg once daily). The patients were treated until disease progression. The primary end point of interest was investigator-assessed radiologic progression-free survival. HRRm status was assessed using optional tumor (n=68), whole blood, and plasma samples.

Overall, there was a statistically significant increase in radiologic progression-free survival in the combination group compared with the comparator group (P=.03). The radiologic progression-free survival benefit was suggested in the combination arm irrespective of HRRm status.

Median overall survival was 23.3 months in the combination arm compared with 20.9 months in the comparator arm (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.58-1.31). Adverse events grade ≥3 were seen in 54% of the combination arm versus 28% of the comparator arm; serious adverse events were reported in 34% of the combination arm versus 18% of the comparator arm. Median time to decline in quality of life was 5.7 months in the combination arm compared with 6.0 months in the comparator arm (HR, 0.97; 95% CI, 0.68-1.40).

In summary, the researchers said, “This is the first trial to show clinical benefit for mCRPC patients treated with a PARP inhibitor combined with abiraterone, regardless of HRRm status. Safety data were less favorable for the combination, but no detriment to quality of life was seen. Our study indicates synergy between olaparib and abiraterone.”

Clinical trial information: NCT01972217

Source: Clarke N, Wiechno PJ, Alekseev B, et al. Olaparib combined with abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A randomized phase II trial. Abstract of an oral session presented at the American Society of Clinical Oncology 2018 Annual Meeting, June 4, 2018, Chicago, Illinois.