Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations.

摘要: Abstract Background Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, are being explored a treatment option for metastatic castration-resistant prostate cancer (mCRPC) in men harboring mutations homologous recombination DNA-repair genes. Whether responses to PARP inhibitors differ according the affected gene is currently unknown. Objective To determine whether between with BRCA1/2 and those ATM mutations. Design, setting, participants This was multicenter retrospective review of 23 consecutive mCRPC pathogenic germline and/or somatic or treated olaparib at three academic sites USA. Outcome measurements statistical analysis The proportion patients achieving ≥50% decline prostate-specific antigen (PSA50 response) compared using Fisher's exact test. Clinical radiographic progression-free survival (PFS) overall were estimated Kaplan-Meier analyses log-rank Results limitations study included two BRCA1 mutations, 15 BRCA2 six PSA50 achieved 76% (13/17) versus 0% (0/6) (Fisher's test; p = 0.002). Patients had median PFS 12.3 mo 2.4 mo (hazard ratio 0.17, 95% confidence interval 0.05–0.57; p = 0.004). Limitations include design relatively small sample size. Conclusions Men experienced inferior outcomes inhibitor therapy Alternative therapies should be Patient summary Mutations genes common cancer. In this we olaparib. We found that do not respond well