Real‐World Outcomes of Olaparib in Japanese Patients With BRCA ‐Mutated Metastatic Castration‐Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status

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ABSTRACT Objectives Metastatic castration‐resistant prostate cancer has a poor prognosis. Although olaparib has demonstrated efficacy in patients with BRCA1/2 mutations, real‐world data in Japanese patients remain limited. We aimed to evaluate the efficacy and safety of olaparib in patients with BRCA‐mutated metastatic castration‐resistant prostate cancer and explore the association of BRCA2 loss and microsatellite instability status with treatment outcomes. Methods We conducted a multicenter retrospective study of 34 patients with BRCA‐mutated metastatic castration‐resistant prostate cancer treated with olaparib between December 2020 and December 2024. The primary endpoint was progression‐free survival. Secondary endpoints included overall survival, prostate‐specific antigen‐50 response rate, and safety. Exploratory analyses were performed. Results Among the 34 patients, 33 had a BRCA2 mutation and one had a BRCA1 mutation. Prostate‐specific antigen reduction was observed in 76.4% of patients; prostate‐specific antigen‐50 response rate was 58.8%. Median progression‐free and overall survival were 15.8 and 35.1 months, respectively. Grade ≥ 3 adverse events (most commonly anemia) occurred in 17.6% of patients. Treatment discontinuation due to adverse events occurred in one patient. Exploratory analyses were performed in 23 BRCA2 ‐mutated patients who underwent comprehensive genomic profiling. BRCA2 loss was observed in 39.1% of patients and showed a trend toward prolonged progression‐free survival, whereas microsatellite instability‐high status was observed in 13.0% and was associated with shorter progression‐free survival. Conclusions Olaparib demonstrated efficacy and safety in Japanese patients with BRCA‐mutated metastatic castration‐resistant prostate cancer. Exploratory analyses revealed that BRCA2 loss may be associated with prolonged progression‐free survival, whereas microsatellite instability‐high status may be associated with shorter progression‐free survival. These findings require validation in larger cohorts.