A 70-year-old man with metastatic castration-resistant prostate cancer (mCRPC) progresses on enzalutamide. Tumour genomic profiling reveals BRCA2 biallelic loss-of-function mutation. Which treatment is most appropriate next?
- A Cabazitaxel chemotherapy
- B Sipuleucel-T immunotherapy
- C Olaparib (PARP inhibitor) ✓
- D Radium-223 dichloride
Correct answer: C. Olaparib (PARP inhibitor)
Explanation
The PROfound trial demonstrated that olaparib, a PARP inhibitor, significantly improved radiographic progression-free survival in patients with mCRPC harbouring BRCA1/2 or ATM alterations who had progressed on enzalutamide or abiraterone. BRCA2 biallelic loss-of-function confers homologous recombination repair deficiency, making PARP inhibitors synthetic lethal. Radium-223 is indicated for bone-metastatic CRPC to extend survival but does not specifically target BRCA-mutant tumours.
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.