Improved Response to Olaparib Treatment Among Men With mCRPC Harboring BRCA1/2 vs ATM Mutations
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, are being explored as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) in men harboring mutations in homologous recombination DNA-repair genes. Whether responses to PARP inhibitors differ according to the affected gene is currently unknown.
OBJECTIVE
To determine whether responses to PARP inhibitors differ between men with BRCA1/2 and those with ATM mutations.
DESIGN, SETTING, AND PARTICIPANTS
This was a multicenter retrospective review of 23 consecutive men with mCRPC and pathogenic germline and/or somatic BRCA1/2 or ATM mutations treated with olaparib at three academic sites in the USA.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The proportion of patients achieving a ≥50% decline in prostate-specific antigen (PSA50 response) was compared using Fisher's exact test. Clinical and radiographic progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier analyses and compared using the log-rank test.
RESULTS AND LIMITATIONS
The study included two men with BRCA1 mutations, 15 with BRCA2 mutations, and six with ATM mutations. PSA50 responses to olaparib were achieved in 76% (13/17) of men with BRCA1/2 versus 0% (0/6) of men with ATM mutations (Fisher's exact test; p=0.002). Patients with BRCA1/2 mutations had median PFS of 12.3mo versus 2.4mo for those with ATM mutations (hazard ratio 0.17, 95% confidence interval 0.05-0.57; p=0.004). Limitations include the retrospective design and relatively small sample size.
CONCLUSIONS
Men with mCRPC harboring ATM mutations experienced inferior outcomes to PARP inhibitor therapy compared to those harboring BRCA1/2 mutations. Alternative therapies should be explored for patients with ATM mutations.
PATIENT SUMMARY
Mutations in BRCA1/2 and ATM genes are common in metastatic prostate cancer. In this study we compared outcomes for men with BRCA1/2 mutations to those for men with ATM mutations being treated with olaparib. We found that men with ATM mutations do not respond as well as men with BRCA1/2 mutations.
Additional Info
Differential Response to Olaparib Treatment Among Men With Metastatic Castration-Resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations
Eur Urol Focus 2019 Feb 21;00(00)00, CH Marshall, AO Sokolova, AL McNatty, HH Cheng, MA Eisenberger, AH Bryce, MT Schweizer, ES AntonarakisFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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