Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas

Ondine Becker, Alice Durand, Marion Chevrier, Laetitia Collet, Laurence Gladieff, Florence Joly, Baptiste Sauterey, Christophe Pomel, Hélène Costaz, Patricia Pautier, Cécile Guillemet, Thibault De La Motte Rouge, Renaud Sabatier, Jean Marc Classe, Thierry Petit, Eric Leblanc, Frédéric Marchal, Pierre Emmanuel Colombo, Emmanuel Barranger, Aude Marie SavoyeLise Bosquet, Isabelle Ray-Coquard, Matthieu Carton, Oliver Colomban, Benoit You, Manuel Rodrigues

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    Résumé

    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 12.0 months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, 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.

    langue originaleAnglais
    journalInternational Journal of Gynecological Cancer
    Les DOIs
    étatAccepté/sous presse - 1 janv. 2024

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