A 70-year-old man with metastatic castration-resistant prostate cancer (mCRPC) progresses after docetaxel chemotherapy. His tumor is found to harbor a BRCA2 germline mutation. The most appropriate next-line targeted therapy is:

• A Olaparib (PARP inhibitor) ✓
• B Cabazitaxel chemotherapy
• C Enzalutamide (androgen receptor antagonist)
• D Pembrolizumab (PD-1 inhibitor)

Explanation

Olaparib, a PARP inhibitor, is approved for mCRPC with homologous recombination repair mutations (BRCA1/2, ATM) following the PROfound trial, which demonstrated significant radiographic progression-free survival improvement over enzalutamide or abiraterone in this biomarker-selected population. PARP inhibitors exploit synthetic lethality in BRCA-deficient tumors. Cabazitaxel is a valid second-line option after docetaxel but lacks biomarker specificity; enzalutamide is used for androgen receptor pathway-driven disease; pembrolizumab is used in TMB-high or MSI-high tumors.

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.