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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.

Takuhisa Nukaya·Taku Naiki·Hiromitsu Watanabe·Keita Nakane·Teruo Inamoto·Takahiro Yasui·Takuya Koie·Kiyoshi Takahara
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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.

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HumansMalePiperazinesProstatic Neoplasms, Castration-ResistantAgedRetrospective StudiesPhthalazinesJapanMiddle AgedMicrosatellite InstabilityMutationBRCA2 ProteinProgression-Free SurvivalTreatment OutcomeAged, 80 and overPoly(ADP-ribose) Polymerase InhibitorsProstate-Specific AntigenBRCA1 ProteinEast Asian PeopleBRCA mutationcomprehensive genomic profilingmetastatic castration‐resistant prostate cancerolaparibpoly (ADP‐ribose) polymerase inhibitorJournal ArticleMulticenter Study

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Takuhisa Nukaya, Taku Naiki, Hiromitsu Watanabe, Keita Nakane, Teruo Inamoto, Takahiro Yasui, Takuya Koie, Kiyoshi Takahara. 2026. 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.. https://doi.org/10.1111/iju.70626

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