Differences in First-Line Chemosensitivity Assessed by ELIMination Rate Constant K in Advanced Serous Ovarian Cancer: Evidence from Western and Japanese Trials in a Gynecologic Cancer InterGroup Meta-Analysis.

OBJECTIVE:Growing evidence suggests potential ethnic and geographical variations in chemotherapy efficacy. The CA125 ELIMination rate constant K score is a pragmatic and reproducible indicator of tumor chemosensitivity in newly diagnosed ovarian cancer. We compared ELIMination rate constant K distributions and prognostic performances between patients enrolled in Japanese and Western trials who had stage III/IV serous ovarian cancer from the Gynecologic Cancer InterGroup individual-patient-data Meta-Analysis in OVarian cancer. METHODS:The ELIMination rate constant K values were previously estimated for 5884 women receiving first-line chemotherapy for ovarian cancer. Data from 246 women enrolled in the Japanese JGOG-3016 trial were compared to 2561 patients from Western trials. ELIMination rate constant K was analyzed as a binary variable (favorable ≥1.0 vs unfavorable <1.0). Prognostic value for progression-free survival and overall survival was assessed using univariable and multi-variable models. A standardization cut-off specific to patients enrolled in the Japanese trial was explored using maximally selected rank statistics. RESULTS:KELIM was significantly higher in patients enrolled in the Japanese trial (median 0.071 day-1 vs 0.056 day-1; p <.0001). Using the standard cut-off, favorable ELIMination rate constant K was independently associated with improved progression-free survival (hazard ratio 0.59, 95% confidence interval 0.43 to 0.83) and overall survival (hazard ratio 0.53, 95% confidence interval 0.36 to 0.79) in patients from the Japanese trial. Applying the exploratory cut-off of 0.07 day-1 strengthened prognostic discrimination (progression-free survival: hazard ratio 0.35, 95% confidence interval 0.25 to 0.49, p <.0001; overall survival: hazard ratio 0.40, 95% confidence interval 0.26 to 0.61, p <.0001). CONCLUSIONS:Potential higher ELIMination rate constant K-assessed chemosensitivity is suggested in patients from Japan with advanced serous ovarian cancer, warranting further prospective validation and investigation into underlying biological and environmental determinants and implications for personalized therapeutic strategies.