Abstract 304P
Background
Among MBC patients with germline breast cancer predisposing mutations, more than 60% have an ER+/HER2- subtype. For these patients, the best therapeutic strategy within the use of endocrine therapy (ET) + CDK4-6 inhibitors, chemotherapy and eventually PARP inhibitors is still to determine.
Methods
PADA-1 (NCT03079011) is a randomized phase III trial testing the clinical utility of real time ESR1 mut detection in the blood of patients treated with AI+P as first line metastatic treatment. In a subsidiary analysis of this trial, we report on the characteristics and outcome of known germline BRCA (1/2) or PALB2 mutation carriers included in the trial.
Results
From 2017/03 to 2019/01, 1017 MBC patients have been included in 83 centers. BRCA1-2/PALB2 status was distributed as follows: mutated in any of the 3 genes (N=20; 2 %; Group A), wild type or variants of uncertain significance (N=125; 12.3%; Group B), non-tested (N=872; 85.7%; Group C). BRCA2 mutation was predominant (n=16) while BRCA1 (n=3) and PALB2 (n=1) were rare. Patients with BRCA1-2/PALB2 (group A) had a median age of 47.1y and were mostly premenopausal (70%). Adjuvant chemotherapy and ET was delivered in 65% and 55% of BRCA1-2/PALB2 mutated patients. With a median follow-up of 21.2m (95% CI [0;34]), median PFS with AI+ P was 14.3m (95%IC [10.4-NR]) in mutation carriers (group A) versus 26.7m (95%IC [24.1-29.4]) in groups B + C (p=0.056). The cumulative incidence of ESR1 mutation emergence during the course of first line was significantly higher in BRCA1-2 PALB2 mutation carriers (Fine & Gray method p=0.03).
Conclusions
In this exploratory analysis, BRCA1-2 PALB2 mutation carriers with HR+/HER2- MBC seem might derive less benefit of AI+P than non-mutated patients. Emergence of ESR1 mutation is a frequent biological event in this subset of patients.
Clinical trial identification
NCT03079011.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer.
Funding
Pfizer.
Disclosure
J-S. Frenel: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: GSK; Advisory/Consultancy: EsaI; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis. F. Dalenc: Officer/Board of Directors: Novartis; Travel/Accommodation/Expenses, Officer/Board of Directors: Pfizer; Officer/Board of Directors: Roche. B. Pistilli: Advisory/Consultancy: Puma Biothechnology; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Myriad Genetics; Speaker Bureau/Expert testimony: MSD Oncology; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pfizer. M-A. Mouret-Reynier: Officer/Board of Directors: Pfizer; Officer/Board of Directors: Roche; Officer/Board of Directors: MSD; Officer/Board of Directors: Lilly; Officer/Board of Directors: Novartis; Officer/Board of Directors: AstraZeneca; Officer/Board of Directors: Myriad. A-C. Hardy-Bessard: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: MSD. T. Bachelot: Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Seattle; Honoraria (self): Genetics. S. Delaloge: Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (institution), Research grant/Funding (institution): Sanofi; Honoraria (institution): Pierre Fabre ; Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution), Research grant/Funding (institution): Puma; Honoraria (institution): Servier; Research grant/Funding (institution): Orion; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): MSD. F.C. Bidard: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Radius; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.