Clinical genitourinary cancer · 2026
Evaluation of Efficacy and Safety of Olaparib in Combination With Abiraterone for the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Homologous Recombination Repair Gene Mutations.
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Wang YiShui, Zhan PengCheng
Аннотация
INTRODUCTION: Metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) gene mutations remains a therapeutic challenge, particularly after progression on prior androgen receptor pathway inhibitors. This study aimed to evaluate the efficacy and safety of olaparib plus abiraterone versus olaparib monotherapy in this specific population.
PATIENTS AND METHODS: This single-center retrospective cohort study included patients with HRR-mutated mCRPC who received olaparib-based therapy between January 2017 and December 2025. Patients were divided into the olaparib monotherapy group and the olaparib plus abiraterone combination group based on the treatment regimen after progression. Prostate-specific antigen (PSA) response (≥50% and ≥90% decline), time to PSA response, radiographic progression-free survival (rPFS), overall survival (OS), and adverse events were assessed.
RESULTS: A total of 174 patients were enrolled, with 98 receiving olaparib monotherapy and 76 receiving combination therapy. The combination group achieved significantly higher PSA50 (68.42% vs. 47.96%, P = .007) and PSA90 (42.11% vs. 22.45%, P = .005) rates, with shorter time to PSA response (7.66 ± 2.29 vs. 9.31 ± 2.48 weeks, P < .001). Mean rPFS (12.19 ± 4.05 vs. 8.63 ± 3.24 months, P < .001) and mean OS (25.33 ± 6.12 vs. 20.91 ± 5.86 months, P < .001) were significantly prolonged with combination therapy. Adverse events, particularly fatigue, anemia, and hypertension, were more frequent in the combination group.
CONCLUSION: In patients with HRR-mutated mCRPC previously treated with abiraterone, continued abiraterone combined with olaparib was associated with superior biochemical and survival outcomes compared with olaparib monotherapy, albeit with increased toxicity. These findings support the potential therapeutic benefit of sustained dual PARP and androgen receptor pathway inhibition in this molecularly defined population.
PATIENTS AND METHODS: This single-center retrospective cohort study included patients with HRR-mutated mCRPC who received olaparib-based therapy between January 2017 and December 2025. Patients were divided into the olaparib monotherapy group and the olaparib plus abiraterone combination group based on the treatment regimen after progression. Prostate-specific antigen (PSA) response (≥50% and ≥90% decline), time to PSA response, radiographic progression-free survival (rPFS), overall survival (OS), and adverse events were assessed.
RESULTS: A total of 174 patients were enrolled, with 98 receiving olaparib monotherapy and 76 receiving combination therapy. The combination group achieved significantly higher PSA50 (68.42% vs. 47.96%, P = .007) and PSA90 (42.11% vs. 22.45%, P = .005) rates, with shorter time to PSA response (7.66 ± 2.29 vs. 9.31 ± 2.48 weeks, P < .001). Mean rPFS (12.19 ± 4.05 vs. 8.63 ± 3.24 months, P < .001) and mean OS (25.33 ± 6.12 vs. 20.91 ± 5.86 months, P < .001) were significantly prolonged with combination therapy. Adverse events, particularly fatigue, anemia, and hypertension, were more frequent in the combination group.
CONCLUSION: In patients with HRR-mutated mCRPC previously treated with abiraterone, continued abiraterone combined with olaparib was associated with superior biochemical and survival outcomes compared with olaparib monotherapy, albeit with increased toxicity. These findings support the potential therapeutic benefit of sustained dual PARP and androgen receptor pathway inhibition in this molecularly defined population.