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 mutations are associated with platinum sensitivity, the relationship between status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between 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 and KELIM, and their impacts on progression-free survival and overall survival.
Results: -mutated m) patients had higher standardized KELIM than -wild type (wt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of in multivariate analyses. KELIM score and could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both wt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either m and unfavorable KELIM, or wt 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 m 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 and discriminates different prognoses within m or wt patients. Patients with both wt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.
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