Dynamic modeling in ovarian cancer: an original approach linking early changes in modeled longitudinal CA-125 kinetics and survival to help decisions in early drug development

Gynecol Oncol. 2014 Jun;133(3):460-6. doi: 10.1016/j.ygyno.2014.04.003. Epub 2014 Apr 12.


Objective: Early prediction of the expected benefit of treatment in recurrent ovarian cancer (ROC) patients may help in drug development decisions. The actual value of 50% CA-125 decrease is being reconsidered. The main objective of the present study was to quantify the links between longitudinal assessments of CA-125 kinetics and progression-free survival (PFS) in treated recurrent ovarian cancer (ROC) patients.

Methods: The CALYPSO randomized phase III trial database comparing two platinum-based regimens in ROC patients was randomly split into a "learning dataset" and a "validation dataset". A parametric survival model was developed to associate longitudinal modeled CA-125 changes (ΔCA125), predictive factors, and PFS. The predictive performance of the model was evaluated with simulations.

Results: The PFS of 534 ROC patients were properly characterized by a parametric mathematical model. The modeled ΔCA125 from baseline to week 6 was a better predictor of PFS than the modeled fractional change in tumor size. Simulations confirmed the model's predictive performance.

Conclusions: We present the first parametric survival model quantifying the relationship between PFS and longitudinal CA-125 kinetics in treated ROC patients. The model enabled calculation of the increase in ΔCA125 required to observe a predetermined benefit in PFS to compare therapeutic strategies in populations. Therefore, ΔCA125 may be a predictive marker of the expected gain in PFS and an early predictive tool in drug development decisions.

Keywords: CA-125; Drug development; Ovarian cancer; Progression-free survival.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • CA-125 Antigen / metabolism*
  • Carboplatin / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Discovery
  • Female
  • Humans
  • Kinetics
  • Middle Aged
  • Models, Statistical
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / mortality
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Paclitaxel / administration & dosage
  • Polyethylene Glycols / administration & dosage
  • Treatment Outcome


  • Biomarkers, Tumor
  • CA-125 Antigen
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • Carboplatin
  • Paclitaxel