Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas
- PMID: 39481880
- DOI: 10.1136/ijgc-2024-005815
Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas
Abstract
Objective: Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values.
Methods: We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival.
Results: BRCA-mutated (BRCAm) patients had higher standardized KELIM than BRCA-wild type (BRCAwt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCAwt and unfavorable KELIM (median progression-free survival 12.0months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCAm and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001).
Conclusions: The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCAm or BRCAwt patients. Patients with both BRCAwt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.
Keywords: BRCA mutation; Chemosensitivity; High-grade serous ovarian carcinoma; KELIM; Platinum-based chemotherapy.
Copyright © 2025. Published by Elsevier Inc.
Conflict of interest statement
Declaration of Competing Interests J-MC: reports personal fees from AstraZeneca, Roche, Vifor, Clovis, GlaxoSmithKline, and Merck Sharp and Dohme, outside the submitted work. LC: reports non-financial support from Pharmamar and GSK, outside the submitted work. P-EC: reports personal fees from Merck Sharp and Dohme, AstraZeneca, and GlaxoSmithKline, outside the submitted work. AD: reports non-financial support from Monaco Age Oncologie, outside the submitted work. TMR: reports personal fees from Pfizer, AstraZeneca, GlaxoSmithKline, Clovis Oncology, Roche, Merck Sharp and Dohme, Mylan, Tesaro, and Norvartis; grants from Pfizer, Merck Sharp and Dohme, and Seagen; a non-financial advisory role for the French National Cancer Institute, Arcagy, and Unicancer, outside the submitted work. LG: reports personal fees from Viatris, Roche, Merck Sharp and Dohme, Clovis, GlaxoSmithKline, and AstraZeneca, outside the submitted work. FJ: reports personal fees from Amgen, Astellas, AstraZeneca, Byaer, EISAI, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp and Dohme, Novartis, Novocure, Pfizer, Seagen, and Viatris; non-financial support from Astellas, AstraZeneca, Bristol-Meyer Squibb, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Ipsen, EISAI, and Chugai, outside the submitted work. EL: reports personal fees from Strycker, outside the submitted work. PP: reports personal fees from GlaxoSmithKline, Merck Sharp and Dohme, PharmaMar, and Roche, outside the submitted work. CP: reports personal fees from Roche, GlaxoSmithKline, Pharmamar, and Merck Sharp and Dohme, outside the submitted work. RS: reports grants from AstraZeneca; personal fees from GlaxoSmithKline, EISAI, Seagen, and Novartis; non-financial support from Merck Sharp and Dohme, GlaxoSmithKline, and Novartis, outside the submitted work. IR-C: reports personal fees from Agenus, Amgen, AstraZeneca, Clovis, Deciphera, GlaxoSmithKline, Macrogenics, Merck Sereno, Mersena, Novartis, Oxnea, Roche, Bristol-Meyer Squibb, and Merck Sharp and Dohme, outside the submitted work. MR: reports non-financial support from AstraZeneca; grants from Merck Sharp and Dohme, Daiichi Sankyo, and Bristol-Meyer Squibb; personal fees from AstraZeneca, Immunocore, Merck Sharp and Dohme, and GlaxoSmithKline, outside the submitted work. BY: reports personal fees from Merck Sharp and Dohme, AstraZeneca, GSK-TESARO, Bayer, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, Bristol-Meyer Squibb, Seagen, Myriad, Menarini, Gilead, and EISAI, outside the submitted work. EB, OB, LB, MCa, MCh, OC, HC, CG, FM, TP, BS, and A-MS have nothing to disclose.
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