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

Pauline Corbaux; Benoit You; Iain McNeish; Stephen Welch; Anna V Tinker; Mansoor R Mirza; Kristina Lindemann; Tatsuo Kagimura; Isabelle L Ray-Coquard; Fabien Subtil; Julien Péron; Karen Carty; Caroline Kelly; Olivier Colomban; Eleni Karamouza; Adrian Cook; Xavier Paoletti; Rosalind M Glasspool; Nozomu Yanaihara

doi:10.1016/j.ijgc.2026.104805

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

Int J Gynecol Cancer. 2026 Jun 16;36(9):104805. doi: 10.1016/j.ijgc.2026.104805. Online ahead of print.

Authors

Pauline Corbaux¹, Benoit You², Iain McNeish³, Stephen Welch⁴, Anna V Tinker⁵, Mansoor R Mirza⁶, Kristina Lindemann⁷, Tatsuo Kagimura⁸, Isabelle L Ray-Coquard⁹, Fabien Subtil¹⁰, Julien Péron¹¹, Karen Carty¹², Caroline Kelly¹², Olivier Colomban¹³, Eleni Karamouza¹⁴, Adrian Cook¹⁵, Xavier Paoletti¹⁶, Rosalind M Glasspool¹⁷, Nozomu Yanaihara¹⁸

Affiliations

¹ Claude Bernard University Lyon 1, Faculty of Medicine Lyon-Sud, Centre pour l'lnnovation en Cancérologie de Lyon (CICLY), Lyon, France; GINECO, CHU de Saint-Etienne, Institut de Cancérologie et d'Hématologie Universitaire de Saint-Etienne, Medical Oncology, Saint-Etienne, France.
² Claude Bernard University Lyon 1, Faculty of Medicine Lyon-Sud, Centre pour l'lnnovation en Cancérologie de Lyon (CICLY), Lyon, France; GINEGEPS, GINECO, Centre Hospitalier Lyon-Sud, CITOHL, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Medical Oncology, Lyon, France. Electronic address: benoit.you@chu-lyon.fr.
³ Imperial College London, Department of Surgery and Cancer, London, United Kingdom.
⁴ London Health Sciences Centre, London, ON, Canada.
⁵ BC Cancer - Vancouver, Vancouver, BC, Canada.
⁶ Nordic Society of Gynecological Oncology, Copenhagen, Denmark; Copenhagen University Hospital, Rigshospitalet, Department of Oncology, Copenhagen, Denmark.
⁷ Norwegian Radium Hospital, Oslo, Norway.
⁸ Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan.
⁹ Inserm U1290 Claude Bernard University Lyon 1 GINECO, Centre Léon Bérard, Lyon, France.
¹⁰ Hospices Civils de Lyon, Service de Biostatistique, Lyon, France; Université Claude Bernard Lyon 1, LBBE, UMR 5558, CNRS, VAS, Villeurbanne, France.
¹¹ GINEGEPS, GINECO, Centre Hospitalier Lyon-Sud, CITOHL, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Medical Oncology, Lyon, France; Hospices Civils de Lyon, Service de Biostatistique, Lyon, France; Université Claude Bernard Lyon 1, LBBE, UMR 5558, CNRS, VAS, Villeurbanne, France.
¹² University of Glasgow, Institute of Cancer Sciences, Glasgow Oncology Clinical Trials Unit, Glasgow, United Kingdom.
¹³ Claude Bernard University Lyon 1, Faculty of Medicine Lyon-Sud, Centre pour l'lnnovation en Cancérologie de Lyon (CICLY), Lyon, France.
¹⁴ Université Paris-Saclay, Office of Biostatistics and Epidemiology, Institut Gustave Roussy, Villejuif, France; Inserm, Université Paris-Saclay, CESP U1018, Oncostat, labeled Ligue Contre le Cancer, Villejuif, France.
¹⁵ MRC Clinical Trials Unit at UCL, London, United Kingdom.
¹⁶ Institut Curie, St Cloud, France.
¹⁷ Beatson West of Scotland Cancer Centre, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom; University of Glasgow, School of Cancer Sciences, Glasgow, United Kingdom.
¹⁸ The Jikei University School of Medicine, Tokyo, Japan.

PMID: 42425044
DOI: 10.1016/j.ijgc.2026.104805

Abstract

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.

Keywords: CA125 KELIM; Chemosensitivity; Epithelial Ovarian Cancer; Ethnicity; Prognostic Biomarker.