[OLAPARIB TREATMENT IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WITH BRCA2 MUTATION AND HIGH TUMOR MUTATIONAL...

In recent years, pharmacologic treatment for advanced prostate cancer has included novel hormonal agents and chemotherapeutic drugs from the initial stages. When resistance develops, personalized therapy based on genomic profiling has become increasingly common. We report a case of castration-resistant prostate cancer (CRPC) with both a BRCA2 mutation and high tumor mutational burden (TMB-high), in which olaparib produced a temporary response. The patient had received hormone therapy, radiotherapy, and chemotherapy, all of which became ineffective. Based on companion diagnostic testing, both olaparib and pembrolizumab were deemed appropriate. Olaparib was administered first, resulting in a decrease in PSA levels maintained for approximately nine months. After PSA re-elevation, pembrolizumab was introduced, but the disease progressed, and the patient died about four months after olaparib discontinuation. Treatment decisions were guided by anticipated response and the low immunogenicity of prostate cancer. This case underscores the potential of biomarker-guided therapy in CRPC and the need to optimize the sequencing and timing of available treatments.