The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: Data from CALYPSO trial (a GINECO-GCIG study)

Benoit You, Olivier Colomban, Mark Heywood, Chee Lee, Margaret Davy, Nicholas Reed, Sandro Pignata, Nenzi Varsellona, Günter Emons, Khalid Rehman, Karina Dahl Steffensen, Alexander Reinthaller, Eric Pujade-Lauraine, Amit Oza

Research output: Contribution to journalArticle

Abstract

Background Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters. Methods Data from CALYPSO phase III trial comparing 2 carboplatin-based regimens in ROC patients were analyzed. Based on population kinetic approach, serum [CA-125] concentration-time profiles during first 50 treatment days were fit to a semi-mechanistic model with following parameters: "d[CA-125] / dt = (KPROD â̂ - exp (BETA â̂ - t)) â̂ - Effect - KELIM â̂ - [CA-125]" with time, t; tumor growth rate, BETA; CA-125 tumor production rate, KPROD; CA-125 elimination rate, KELIM and K-dependent treatment indirect Effect. The predictive values of kinetic parameters were tested regarding progression-free survival (PFS) against other reported prognostic factors. Results Individual CA-125 kinetic profiles from 895 patients were modeled. Three kinetic parameters categorized by medians had predictive values using univariate analyses: K; KPROD and KELIM (all P <0.001). Using Cox multivariate analysis, 5 independent predictors of PFS remained significant: GCIG CA-125 response (favoring carboplatin-paclitaxel arm), treatment arm, platinum free-interval, measurable lesions and KELIM (HR = 0.53; 95% CI 0.45-0.61; P <0.001). Conclusions Mathematical modeling of CA-125 kinetics in ROC patients enables understanding of the time-change components during chemotherapy. The contradictory surrogacy of GCIG-defined CA-125 response was confirmed. The modeled CA-125 elimination rate KELIM, potentially assessable in routine, may have promising predictive value regarding PFS. Further validation of this predictive marker is warranted.

Original languageEnglish
Pages (from-to)289-294
Number of pages6
JournalGynecologic Oncology
Volume130
Issue number2
DOIs
Publication statusPublished - Aug 2013

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Keywords

  • CA-125 antigen Kinetics Ovarian epithelial cancer Survival analysis Computer simulation

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

You, B., Colomban, O., Heywood, M., Lee, C., Davy, M., Reed, N., Pignata, S., Varsellona, N., Emons, G., Rehman, K., Steffensen, K. D., Reinthaller, A., Pujade-Lauraine, E., & Oza, A. (2013). The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: Data from CALYPSO trial (a GINECO-GCIG study). Gynecologic Oncology, 130(2), 289-294. https://doi.org/10.1016/j.ygyno.2013.05.013