DNA Repair Gene Alterations and PARP Inhibitor Response in Patients With Metastatic Castration-Resistant Prostate Cancer

• DOI: 10.6004/jnccn.2018.7020
• Publication Date: 2018-08-11T21:15:16Z
• Authors: Eric Lu; George V. Thomas; Yiyi Chen; Alexander W. Wyatt; Paul Lloyd; Jack Youngren; David Quigley; Raymond Bergan; Shawna Bailey; Tomasz M. Beer; Felix Y. Feng; Eric J. Small; Joshi J. Alumkal
• Keywords: PARP inhibitor

Background: PARP inhibition is a promising therapeutic strategy for the treatment of men with metastatic castration-resistant prostate cancer whose tumors harbor homologous recombination DNA repair gene alterations. However, questions remain many practicing clinicians about which patients are ideally suited inhibitor treatment. This report details our institutional experience using therapy in harbored specific Patients and Methods: We performed retrospective chart review to identify at Oregon Health & Science University who were treated inhibition. identified 8 determined impact alterations on tumor response time Results: A number identified. Three had pathogenic BRCA2 mutations one mutation uncertain significance. Conversely, 4 other patients' genes, none clearly pathogenic. statistically significant difference benefit was seen between those did not, as measured by >50% decline prostate-specific antigen levels (100% vs 0%; P=.03) duration (31.4 6.4 weeks; P=.03). Conclusions: Our results demonstrate that not all equally predictive response. Importantly, responding harboring alterations, including without known mutation. among nonresponders, several genes than demonstrates need carefully examine functional relevance identified, especially BRCA2, when considering