Abstract 53P
Background
High-grade epithelial ovarian cancer (HGOC) harboring a BRCA mutation (BRCAm) are the proof of concept for a homologous recombination deficient tumor. As a result of this defect in a crucial DNA repair pathway, most BRCAm OC are sensitive to first-line platinum-based chemotherapy. However, a small subset of patients (pts) with BRCAm OC demonstrate primary chemo-resistance. We aimed to describe the prevalence, clinico-pathological characteristics, and disease evolution of pts with primary resistant/refractory BRCAm OC (PROC).
Methods
We conducted a retrospective observational cohort study based on OC data from the Epidemiological Strategy and Medical Economics (ESME) platform which centralizes real-life data of pts aged ≥ 18 years treated for OC in France between 2011 and 2022. PROC was defined as pts who received non-platinum chemotherapy in second-line for progression.
Results
Out of the 13,032 pts included in the ESME database, 1505 pts with BRCAm HGOC were identified. The prevalence of PROC among pts with BRCAm OC was 3.3% (43/1302). When comparing BRCAm PROC and BRCAm platinum sensitive OC (PSOC) pts, there were no significant differences in age at diagnosis (p=0.1798), but there was a trend in distribution of BRCA1(77 vs 66%) vs BRCA2 (21 vs 34%) mutations (p=0.0687). BRCAm PROC was more frequently associated with non-serous histology (29% vs 16%, p=0.042), with higher FIGO stage at diagnosis (85% vs 41% stage IV, p=0.0003), and non-operable disease at diagnosis (77% vs 55%, p= 0.004). Pts with BRCAm PROC had higher ca125 values at diagnosis and at last platinum than PSOC patients (mean 3364 vs 2090, p=0.04, and 562 vs 51U/mL, p<0.0001, respectively). Median PFS and OS were 10.2 [7.6-11.7] and 29.2 months [19.0-43.2] respectively in BRCAm PROC pts, and 34.0 [31.9-36.8] and 95.1 months [88.0-104.9] in PSOC pts.
Conclusions
PROC is rare among pts with BRCAm OC but their prognosis is catastrophic. BRCAm PROC pts were more likely to have non-serous histology and exhibited more advanced disease at diagnosis than PSOC pts. We did not identify any other predominant features distinguishing PROC pts. These results suggest the importance of early cancer screening in BRCAm pts.
Legal entity responsible for the study
Unicancer manages independently ESME OC database (i.e., data collection, analyses and publication) and is the sole data controller for data processing. This study was specifically conducted by Alexandra Leary (Gustave Roussy).
Funding
The ESME Ovarian Cancer database (NCT03275298) received financial support from industrial partners. Unicancer manages the database (i.e., data collection, analyses and publication) independently.
Disclosure
A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape, Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AstraZeneca, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: Owkin; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AstraZeneca; Financial Interests, Institutional, Funding, CI clinical trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AstraZeneca; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer; Non-Financial Interests, Personal, Member: GCIG. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, Sutro, BMS, Adaptimmune, Daiichi Sankyo, Immunogen, Seagen, PMVpharma; Financial Interests, Institutional, Other, Colibri translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Personal, Principal Investigator: PAOLA1; Non-Financial Interests, Personal, Other, President: GINECO. M.J. Rodrigues: Financial Interests, Personal, Invited Speaker: Immunocore; Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Johnson & Johnson; Non-Financial Interests, Institutional, Product Samples: MSD. J. Frenel: Financial Interests, Personal, Advisory Board: Pfizer, Novocure, Pierre Fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, Amgen, Eisai, AstraZeneca, Seagen, MSD, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Exact Sciences, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Non-Financial Interests, Personal, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD. R. Sabatier: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: Eisai, Clovis Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Personal, Other, Travel fees: MSD, Novartis; Non-Financial Interests, Personal, Other, Congress fees: GSK. T. De La Motte Rouge: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, GSK, Clovis oncology, Roche, MSD, Mylan, Tesaro, Gilead, Sanofi, Seagen; Financial Interests, Personal, Invited Speaker: Novartis, MSD; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, MSD, Seagen; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, GSK, MSD, Pfizer, Netris Pharma; Non-Financial Interests, Personal, Advisory Role: French National Cancer Institute, Unicancer; Non-Financial Interests, Personal, Principal Investigator: Arcagy, Unicancer; Non-Financial Interests, Personal, Other, Co-Principal Investigator: Unicancer; Non-Financial Interests, Personal, Other, partnership using a Natera solution for a clinical trial funded by academic grant: Natera. P. Colombo: Financial Interests, Personal, Invited Speaker: GSK, MSD. C. Pomel: Financial Interests, Personal, Advisory Board: Roche, GSK, PharmaMar, MSD; Financial Interests, Personal, Invited Speaker: Roche, GSK, PharmaMar; Financial Interests, Personal, Expert Testimony: Roche. C. Lebreton: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Expert Testimony: GSK, MSD, Eisai, Clovis oncology. L. Bosquet: Financial Interests, Institutional, Full or part-time Employment, In charge of scientific projects at Unicancer, Health Data and Partnership Department: Unicancer. L. Gladieff: Financial Interests, Personal, Other, Congress funding: Viatris, Roche; Financial Interests, Institutional, Invited Speaker: MSD, Clovis, GSK, Eisai; Financial Interests, Institutional, Advisory Board: Clovis, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca. All other authors have declared no conflicts of interest.