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).

TitleThe strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: data from CALYPSO trial (a GINECO-GCIG study).
Publication TypeJournal Article
Year of Publication2013
AuthorsYou, B, Colomban, O, Heywood, M, Lee, C, Davy, M, Reed, NSimon, Pignata, S, Varsellona, N, Emons, G, Rehman, K, Steffensen, KDahl, Reinthaller, A, Pujade-Lauraine, E, Oza, AM
JournalGynecol Oncol
Volume130
Start Page289
Issue2
Pagination294
Date Published08/2013
ISSN1095-6859
KeywordsCA-125 Antigen, Disease-Free Survival, Female, Humans, Kinetics, Models, Theoretical, Neoplasm Recurrence, Local, Ovarian Neoplasms, Prognosis, Proportional Hazards Models
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∗exp (BETA∗t))∗Effect-KELIM∗[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.

DOI10.1016/j.ygyno.2013.05.013
Alternate JournalGynecol. Oncol.
PubMed ID23694718