Olaparib combined with abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A randomized phase II trial.

5003 Background: mCRPC pts with a homologous recombination repair mutation (HRRm) previously showed improved response to the PARP inhibitor olaparib (Lynparza) as monotherapy vs pts without a HRRm (Mateo J et al, NEJM 2015). We report data from a Phase II, placebo-controlled trial of olaparib combined with the anti-hormonal therapy abiraterone in post-chemotherapy mCRPC pts whose tumors did not need to have a HRRm (NCT01972217). Methods: mCRPC pts were randomized (1:1) post-docetaxel to olaparib 300 mg bid (tablets; combination) or placebo (comparator) plus abiraterone (1000 mg od) and treated until disease progression. Primary endpoint was investigator-assessed radiologic progression-free survival (rPFS; RECIST 1.1, PCWG-2). HRRm status was assessed using optional tumor (n = 68), whole-blood and plasma samples. Results: 142 pts (median age: 69 yrs) were randomized and treated (both arms, n = 71). Overall, a statistically significant increase in rPFS was seen with the combination vs comparator (Table; P= 0.03). A rPFS benefit in the combination arm was suggested irrespective of HRRm status. Median overall survival was 23.3 vs 20.9 mths in the combination vs comparator arms, respectively (HR 0.89, 95% CI 0.58–1.35). 54% vs 28% of pts, respectively, had grade ≥3 AEs; 34% vs 18% reported serious AEs, including more cardiovascular AEs with the combination. 30% vs 10% of pts, respectively, discontinued treatment due to an AE. Median time to deterioration in quality of life (QoL; FACT-P) was 5.7 vs 6.0 mths, respectively (HR 0.97, 95% CI 0.68–1.40). Conclusions: This is the first trial to show clinical benefit for mCRPC pts treated with a PARP inhibitor combined with abiraterone, regardless of HRRm status. Safety data were less favorable for the combination, but no detriment to QoL was seen. Our study indicates synergy between olaparib and abiraterone. Clinical trial information: NCT01972217.rPFS by HRRm status. Pt group Median rPFS,* mths (combination vs comparator) HR (95% CI) Overall, n = 142 13.8 vs 8.2 0.65 (0.44–0.97) HRRm, n = 21 17.8 vs 6.5 0.74 (0.26–2.12) HRRwt,† n = 35 15.0 vs 9.7 0.52 (0.24–1.15) HRRm unknown, n = 86 13.1 vs 6.4 0.67 (0.40–1.13) *Kaplan-Meier method; †tumor test result required. wt, wild-type.