Abstract 596P
Background
CA125 decline, assessed by the CA-125 elimination rate constant K (KELIM) model, and BRCA mutations are associated with chemosensitivity but their interaction has not been explored yet. We here assess the correlation of KELIM and BRCA status in the real-life French ESME OC registry (NCT03275298).
Methods
Data from FIGO stage III/IV HGSOC pts treated with neo-adjuvant chemotherapy were extracted from this registry. KELIM scores were calculated, standardized and scored as unfavorable if ≤ 1 or favorable if >1.
Results
Of the 10,263 pts in the ESME OC cohort, KELIM was assessable for 743 pts meeting the inclusion criteria, including 124 BRCA-mutated (BRCAm) and 324 BRCA-wild type (BRCAwt). Median follow-up was 50.3 months (mo). Median KELIM values were higher in BRCAm pts versus (vs) BRCAwt (median of 1.164 vs 1.057; p=0.001). KELIM scores distribution was bimodal in BRCAm pts corresponding to BRCA1m and BRCA2m (median of 1.148 and 1.213, respectively). However, the distributions of KELIM and BRCA mutations were not superimposable, suggesting they are not interchangeable. In PFS and OS multivariate analyses, FIGO stage, BRCA mutation, KELIM score and use of bevacizumab were significant (except bevacizumab which was associated only with PFS). Pts with favorable KELIM had significantly better PFS and OS than unfavorable (median PFS of 20.0 and 11.0 mo; HR 0.55, p<0.001; median OS of 63.4 and 38.8 mo; HR 0.49, p<0.001). Among BRCAwt pts, those with favorable KELIM had longer PFS than those with unfavorable KELIM (18.8 mo vs 12.0 mo, HR 1.6, p<0.001). Strikingly, PFS of BRCAm pts with favorable KELIM was much longer than those with unfavorable (28.8 mo vs 16.1 mo, HR 2.0, p=0.001) suggesting that pts with poor chemosensitivity experienced shorter PFS despite BRCA status.
Conclusions
KELIM and BRCA statuses are not interchangeable but two complementary prognostic tools in pts with HGSOC. KELIM provides important information on the tumor intrinsic chemosensitivity beyond BRCA status that might help guide the optimal maintenance treatment considering the different options available. Prospective validation is warranted.
Clinical trial identification
NCT03275298.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer.
Funding
The ESME OC database is supported by an industrial consortium (AstraZeneca and GlaxoSmithKline).
Disclosure
L. Gladieff: Financial Interests, Personal, Other, Congress funding: Viatris, Roche; Financial Interests, Institutional, Invited Speaker: MSD, Clovis, GSK; Financial Interests, Institutional, Advisory Board: CloviS, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca. F. Joly Lobbedez: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, GSK, Ipsen, Janssen, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, BMS, Eisai, GSK, Ipsen, Janssen, MSD; Non-Financial Interests, Institutional, Research Grant: BMS; Non-Financial Interests, Institutional, Other, coordinating PI: GSK; Financial Interests, Other, travel: GSK, MSD. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Agenus, Amgen, AstraZeneca, Clovis, Deciphera, GSK, Macrogenics, Merck Sereno, Mersena, Novartis, Oxnea, Roche; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA. C. Pomel: Financial Interests, Personal, Advisory Board: GSK, MSD, PharmaMar, Roche; Financial Interests, Personal, Invited Speaker: GSK, PharmaMar, Roche; Financial Interests, Personal, Expert Testimony: Roche. P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020: Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021: AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Expert Testimony, 2022: MSD. T. De La Motte Rouge: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, GSK, Clovis Oncology, Roche, MSD, Mylan, Tesaro, Norvartis; Financial Interests, Personal, Research Grant: Pfizer, MSD, Seagen; Financial Interests, Personal, Other, Local PI: Roche, AstraZeneca, GSK, MSD, Pfizer, Netris Pharma; Non-Financial Interests, Personal, Advisory Role: French national cancer institute; Non-Financial Interests, Personal, Principal Investigator: ARCAGY; Non-Financial Interests, Advisory Role: Unicancer. R. Sabatier: Financial Interests, Personal, Research Grant: EISAI, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, GSK, EISAI, Novartis; Non-Financial Interests, Personal, Other: Pfizer, Roche, GSK, BMS, AstraZeneca. J. Classe: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Vifor; Financial Interests, Personal, Invited Speaker: Clovis, Glaxo Smith Kline, MSD. E. Leblanc: Financial Interests, Personal, Invited Speaker: Strycker; Non-Financial Interests, Principal Investigator, Fimbriectomie NCT01608074: centre oscar lambret; Non-Financial Interests, Principal Investigator, SENTIRAD15-02 (NCT 02598219): Centre Oscar Lambret. P. Colombo: Financial Interests, Personal, Invited Speaker: GSK. B. You: Financial Interests, Personal, Advisory Board: MSD, Astra-Zeneca, GSK-Tesaro, Bayer, Roche-Genetech, ECS-Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serano, BMS, Seagen, Myriad. M.J. Rodrigues: Financial Interests, Personal, Advisory Board: Astra-Zeneca, GlaxoSmithKline, Merck sharp and Dohme, Immunocore; Financial Interests, Institutional, Advisory Board: Merck sharp and Dohme, Bristol-Meyer Squibb, Daiichi Sankyo. All other authors have declared no conflicts of interest.