Dillon Cockrell: Targeted Therapy for mCRPC with BRCA Mutations
Dillon Cockrell, Medical Oncologist and GU Cancer Expert at Duke Cancer Center, shared an article on LinkedIn:
“Targeted Therapy for mCRPC with BRCA Mutations.
Check out this excellent summary from our Duke Cancer Institute GU team led by Andrew Armstrong and Daniel George diving into the PROfound and PROpel trials, highlighting the importance of genomic testing in castration-resistant prostate cancer (CRPC) and the efficacy of PARP inhibitors (PARPi) like olaparib for BRCA-mutated disease.
Background: ~10-12% of mCRPC patients harbor BRCA mutations. Genomic testing (via circulating tumor DNA or tumor tissue) is needed to identify these patients for personalized therapy.
PROfound Trial (Olaparib Monotherapy):
- Phase 3 trial comparing olaparib vs enzalutamide or abiraterone in HRRm mCRPC patients after ARPI progression (Cohort A: BRCAm/ATMm, n=245).
- rPFS: 9.8 months vs. 3.0 months (HR 0.22, 95% CI 0.15–0.32).
- OS: 20.1 months vs. 14.4 months (HR 0.63, 95% CI 0.42–0.95).
PROpel Trial (Olaparib + Abiraterone):
- Phase 3 trial evaluating olaparib + abi/pred vs placebo + abi/pred in ARPI naive mCRPC patients (BRCAm subgroup, n=85).
- rPFS: Not reached vs. 8.4 months (HR 0.23, 95% CI 0.12–0.43).
- OS: Not reached vs. 23.0 months (HR 0.29, 95% CI 0.14–0.56).
- Time to subsequent therapy: 37.4 months vs. 14.8 months (HR 0.35, 95% CI 0.21-0.61).
Conclusions: Both trials underscore the importance of genomic testing in mCRPC to identify BRCA (and other HRR) mutations in mCRPC patients, as targeted therapies like olaparib can significantly improve outcomes for patients who may otherwise have limited effective treatment options.
Check out the infographic and read the full article here.”
Olaparib Monotherapy or in Combination with Abiraterone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) and a BRCA Mutation.
Authors: Fred Saad, Andrew J. Armstrong, Neal Shore, Daniel J. George, Mototsugu Oya, Mikio Sugimoto, Rana R. McKay, Maha Hussain, and Noel W. Clarke.
You can read the full article on Journal of Springer Nature Link.
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