Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study
AuthorMateo, J; Cheng, HH; Beltran, H; Dolling, D; Xu, W; Pritchard, CC; Mossop, H; Rescigno, P; Perez-Lopez, R; Sailer, V; ...
Source TitleEuropean Urology
PublisherELSEVIER SCIENCE BV
University of Melbourne Author/sSandhu, Shahneen
AffiliationSir Peter MacCallum Department of Oncology
Document TypeJournal Article
CitationsMateo, J., Cheng, H. H., Beltran, H., Dolling, D., Xu, W., Pritchard, C. C., Mossop, H., Rescigno, P., Perez-Lopez, R., Sailer, V., Kolinsky, M., Balasopoulou, A., Bertan, C., Nanus, D. M., Tagawa, S. T., Thorne, H., Montgomery, B., Carreira, S., Sandhu, S. ,... de Bono, J. S. (2018). Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study. EUROPEAN UROLOGY, 73 (5), pp.687-693. https://doi.org/10.1016/j.eururo.2018.01.010.
Access StatusOpen Access
BACKGROUND: Germline DNA damage repair gene mutation (gDDRm) is found in >10% of metastatic prostate cancer (mPC). Their prognostic and predictive impact relating to standard therapies is unclear. OBJECTIVE: To determine whether gDDRm status impacts benefit from established therapies in mPC. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective, international, observational study. Medical records were reviewed for 390 mPC patients with known gDDRm status. All 372 patients from Royal Marsden (UK), Weill-Cornell (NY), and University of Washington (WA) were previously included in a prevalence study (Pritchard, NEJM 2016); the remaining 18 were gBRCA1/2m carriers, from the kConFab consortium, Australia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Response rate (RR), progression-free survival (PFS), and overall survival (OS) data were collected. To account for potential differences between cohorts, a mixed-effect model (Weibull distribution) with random intercept per cohort was used. RESULTS AND LIMITATIONS: The gDDRm status was known for all 390 patients (60 carriers of gDDRm [gDDRm+], including 37 gBRCA2m, and 330 cases not found to carry gDDRm [gDDRm-]); 74% and 69% were treated with docetaxel and abiraterone/enzalutamide, respectively, and 36% received PARP inhibitors (PARPi) and/or platinum. Median OS from castration resistance was similar among groups (3.2 vs 3.0 yr, p=0.73). Median docetaxel PFS for gDDRm+ (6.8 mo) was not significantly different from that for gDDRm- (5.1 mo), and RRs were similar (gDDRm+=61%; gDDRm-=54%). There were no significant differences in median PFS and RR on first-line abiraterone/enzalutamide (gDDRm+=8.3 mo, gDDRm-=8.3 mo; gDDRm+=46%, gDDRm-=56%). Interaction test for PARPi/platinum and gDDRm+ resulted in an OS adjusted hazard ratio of 0.59 (95% confidence interval 0.28-1.25; p=0.17). Results are limited by the retrospective nature of the analysis. CONCLUSIONS: mPC patients with gDDRm appeared to benefit from standard therapies similarly to the overall population; prospective studies are ongoing to investigate the impact of PARPi/platinum. PATIENT SUMMARY: Patients with inherited DNA repair mutations benefit from standard therapies similarly to other metastatic prostate cancer patients.
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