Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis

Corbaux, P. et al. (2023) Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis. European Journal of Cancer, 191, 112966. (doi: 10.1016/j.ejca.2023.112966) (PMID:37542936)

Abstract

Background In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors. Methods: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model. Results: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41–0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45–0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established. Conclusion: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.

• Item Type: Articles
• Additional Information: This work was supported by the Gynaecologic Cancer Intergroup (GCIG), the Groupe d'Investigateurs National des Etudes des Cancers Ovariens et du sein (GINECO), the University Claude Bernard, Lyon 1 and the Hospices Civils de Lyon.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Glasspool, Dr Rosalind and Kelly, Mrs Caroline

Creator Roles

Glasspool, R.: Conceptualization, Funding acquisition, Investigation, Formal analysis, Writing – review and editing
Kelly, C.: Investigation, Writing – review and editing

• Authors: Corbaux, P., You, B., Glasspool, R. M., Yanaihara, N., Tinker, A. V., Lindemann, K., Ray-Coquard, I. L., Mirza, M. R., Subtil, F., Colomban, O., Péron, J., Karamouza, E., McNeish, I., Kelly, C., Kagimura, T., Welch, S., Lewsley, L.-A., Paoletti, X., and Cook, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: European Journal of Cancer
• Publisher: Elsevier
• ISSN: 0959-8049
• ISSN (Online): 1879-0852
• Published Online: 04 July 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in European Journal of Cancer 191:112966
• Publisher Policy: Reproduced under a Creative Commons licence