Abstract 692TiP
Background
Germline BRCA2 mutations (gBRCA2) are associated with poor prognosis in patients (pts) with mCRPC. The PROREPAIR-B study suggested that the choice of 1st-line(L) treatment could affect progression after the next line of therapy (PFS2) and cancer-specific survival (CSS) in gBRCA2 carriers with mCRPC.
Trial design
BRCA2men study aims to establish the potential value of gBRCA2 as a biomarker for treatment decision-making in 1st-L mCRPC and to confirm the prognostic role of gBRCA2 in mCRPC. BRCA2men also aims to explore the clinical implications and prevalence of germline mutations in other DNA damage-response genes (gDDR). Pts in this multi-institutional pooled cohort may be already included in clinical studies or prospective cohorts. Eligible pts are men who: 1) have received at least a 1st-L for mCRPC with abiraterone/enzalutamide (ARSi) or taxane; 2) have available follow-up data for at least 1 year since starting 1L for mCRPC; 3) have a sample amenable for screening germline mutations (constitutive DNA) or available NGS data of whole exome/genome sequencing. To avoid selection bias of best-surviving pts, samples or germline analyses must have been obtained no later than >6 months after starting a 2L for mCRPC. Response data for 1L and 2L, survival outcomes, tumor features, baseline data and family history of cancer will be collected. The primary analysis aims to compare the difference in PFS2 in gBRCA2 carriers treated with 1st-L taxanes versus 1st-L ARSi for mCRPC. Overall, approximately 2000 pts are planned to be included in main (gBRCA2) and exploratory cohorts. In the main analysis cohort, we aim to identify 32 gBRCA2 carriers treated with 1L taxane or ARSi after progression to ADT, not exposed to platinum salts or PARPi. Secondary analyses will include survival outcomes for gBRCA2 pts according to 1st-L treatment. Exploratory analyses will also ascertain the response to therapies and survival of pts with other gDDR mutations. Collected data will also be used to generate a risk-prediction tool to identify pts more likely to carry a gDDR mutation and optimize germline screening.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Biomedical Research Institute of Malaga / Andalusian Public Foundation for Malaga Research in Biomedicine and Health (IBIMA / FIMABIS) Spanish National Cancer Research Centre (CNIO).
Funding
Biomedical Research Institute of Malaga / Andalusian Public Foundation for Malaga Research in Biomedicine and Health (IBIMA / FIMABIS) Spanish National Cancer Research Centre (CNIO).
Disclosure
C. Cattrini: Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Ipsen. R. Lozano Mejorada: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen; Speaker Bureau/Expert testimony: Sanofi; Travel/Accommodation/Expenses: Astellas. V. Conteduca: Honoraria (self), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Travel/Accommodation/Expenses: Janssen-Cilag; Honoraria (self), Travel/Accommodation/Expenses: Sanofi-Aventis; Advisory/Consultancy: Bayer. M.P. Lolkema: Advisory/Consultancy, Research grant/Funding (institution): Johnson & Johnson; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Amgen; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy: Novartis; Advisory/Consultancy: Julius Clinical; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Ipsen. D. Lorente: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas. N. Romero Laorden: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Bayer; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Ipsen; Speaker Bureau/Expert testimony: MSD; Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer. A.A. Azad: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Tolmar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Telix; Honoraria (self), Advisory/Consultancy: Bayer; Research grant/Funding (institution): Aptevo Therapeutics; Research grant/Funding (institution): Glaxo Smith Kline; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): SYNthorx; Research grant/Funding (institution): Bionomics. J. Puente: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Clovis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Eisai; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: Sanofi; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony: Kiowa; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Lilly. N. Mehra: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Sanofi. U. De Giorgi: Advisory/Consultancy: Astellas; Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Roche; Research grant/Funding (institution): Sanofi. D. Olmos Hidalgo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Clovis; Research grant/Funding (institution): Medivation/Pfizer; Research grant/Funding (institution): Tokai; Research grant/Funding (institution): MSD; Research grant/Funding (institution): GSK; Travel/Accommodation/Expenses: Ipsen. E. Castro Marcos: Honoraria (self), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self): Pfizer; Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.