Olaparib combined with abiraterone versus olaparib alone for patients with DNA-repair deficient metastatic castration-resistant prostate cancer after progressing on abiraterone: A multicenter, real-world study.
Authors: Xie Jun , Yang Guanjie , Dong Baijun , Chen Wei , Zhao Tingting , Wang Ruiliang , Ye Lin , Huang Longfei , Liu Tongtong , Zhang Menghuan , Xue Wei , Peng Bo , Yao Xudong , Yang Bin 
Published: June 2022

e17021

Background: Accumulated evidence reports that olaparib has antitumor activity for patients with DNA-repair deficient (DRD) metastatic castration-resistant prostate cancer (mCRPC). Olaparib monotherapy also has significantly longer survival outcomes in patients with DRD mCRPC after progressing on a novel hormonal therapy (NHT) than physician’s choice of another subsequent NHT. In addition, clinical trials indicate that olaparib combined with abiraterone is more effective than abiraterone alone for mCRPC patients irrespective of DRD status. However, the efficacy of olaparib combined with abiraterone in patients with DRD mCRPC after progressing on abiraterone has not been studied. Therefore, we conducted a multicenter, real-world study to compare olaparib combined with abiraterone versus olaparib alone for patients with DRD mCRPC. Methods: A total of 89 mCRPC patients from three Chinese hospitals were retrospectively studied between October 2017 and November 2021. All the patients had disease with progression after abiraterone and with DRD status by a 50-gene panel targeted next-generation sequencing (NGS), including pathogenic, suspected pathogenic, or variants of unknown significance (VUS) in the DNA damage repair (DDR) genes. 35 patients received olaparib combined with abiraterone and 54 olaparib alone. The primary end point included progression-free survival (PFS) and overall survival (OS) which were calculated using Kaplan-Meier methods, and compared using Cox proportional hazards model. The safety was also evaluated. Results: There was no difference in the basline characteristics between the two groups. The median follow-up time was 9 months (range 1-48 months). The median PFS and OS were significantly higher in patients receiving olaparib combined with abiraterone than in those receiving olaparib alone respectively (PFS: 6 vs. 3 months; OS: 24 vs. 12 months, both p < 0.01). Moreover, olaparib combined with abiraterone had a better adjusted hazard ratio of 0.385 (95% CI 0.230-0.643, p < 0.001) and 0.359 (95% CI 0.175-0.737, p = 0.005) as compared to monotherapy in PFS and OS respectively. Some drug-related adverse events, such as nausea and anemia, were reported, and the serious adverse events were rare, which were similar to those previously reported. Conclusions: Olaparib combined with abiraterone had better PFS and OS compared with olaparib alone in Patients with DRD mCRPC after progressing on abiraterone, suggesting a potential synergistic effect of olaparib with abiraterone in clinical settings. Both the combination therapy and monotherapy were relatively well tolerated in the mCRPC patients and the adverse events were within acceptable limits. The results need to be further confirmed by a large-scale prospective randomized controlled trial.