CA125 longitudinal decline kinetic is complementary to BRCA testing in first-line high grade serous ovarian carcinoma (HGSOC) patients (pts)

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). 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. 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. 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.