PROREPAIR-B (NCT03075735) is a prospective, multi-center observational cohort study. Patients diagnosed with mCRPC, with unknown mutational status at study entry and who were going to start a first-line treatment for mCRPC were eligible. For this sub-analysis, patients who received abiraterone or enzalutamide as first androgen receptor targeted therapy were selected. The endpoints of this sub-analysis assessed the impact of BRCA1, BRCA2, ATM, PALB2 and other germline mutations in DNA repair genes on cause-specific survival (CSS), progression-free survival (PFS), time to PSA progression and response to the first androgen receptor targeted therapy received as 1st or 2nd line therapy.
There were 365 patients eligible for this analysis and 57 validated germline DDR defects were detected among these patients (15.6% prevalence). CSS from mCRPC was not significantly different between germline DDR defect carriers and non-carriers. However, CSS from mCRPC in BRCA2 carriers was significantly shorter than in non-carriers (17.5 vs 33.1 months, p = 0.02). CSS from first androgen receptor targeted therapy, PFS and response-rates were not significantly different between both groups. However, time to PSA progression was shorter in patients who were BRCA2 carriers (2.9 vs 7.0 months, p = 0.118), as was PFS (4.2 vs 9.1 months, p = 0.064). On multivariable analysis, BRCA2 was not prognostic for CSS, however elevated LDH, hemoglobin <10 mg/dL and albumin <3.5 g/dL were independent predictors of CSS.
The authors concluded that this is the first study to prospectively follow-up DNA repair germline mutations to determine clinical outcomes of standard treatment for mCRPC. There was a trend to a short cancer-specific survival, time to PSA progression, and progression-free survival from first androgen signaling inhibitor in BRCA2 carriers. The results suggest that different germline DDR defects may have a distinctive impact on mCRPC outcomes.
Presented by: Rebeca Lozano, MD Spanish National Cancer Research Centre, Madrid, Spain
Co-Authors: Nuria Romero-Laorden, Angela del Pozo, Ana Medina, Maria Jose Mendez, Rafael Morales Barrera, Aranzazu Aranzazu Gonzalez del Alba, Alejo Rodriguez-Vida, Amaia Hernandez, Juan Carlos Silla-Castro, Sergio Vazquez, Belen Gonzalez, Alvaro Pinto, Jose Luis Perez Gracia, Rosa Querol, Vanessa Cañadilla, Montserrat Domenech, Colin Pritchard, Elena Castro, David Olmos
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, @zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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