Linking Tumor Growth Dynamics to Survival in Ipilimumab-Treated Patients With Advanced Melanoma Using Mixture Tumor Growth Dynamic Modeling

CPT Pharmacometrics Syst Pharmacol. 2019 Nov;8(11):825-834. doi: 10.1002/psp4.12454. Epub 2019 Aug 13.


Early tumor assessments have been widely used to predict overall survival (OS), with potential application to dose selection and early go/no-go decisions. Most published tumor dynamic models assume a uniform pattern of tumor growth dynamics (TGDs). We developed a mixture TGD model to characterize different patterns of longitudinal tumor sizes. Data from 688 patients with advanced melanoma who received ipilimumab 3 or 10 mg/kg every 3 weeks in a phase III study (NCT01515189) were used in a TGD-OS analysis. The mixture model described TGD profiles using three subpopulations (no-growth, intermediate, and fast). The TGD model showed a positive exposure/dose-response (i.e., a higher proportion of patients in no/intermediate growth subpopulations and a lower tumor growth rate with ipilimumab 10 mg/kg relative to the 3 mg/kg dose). Finally, the mixture TGD model-based measures of tumor response provided better predictions of OS compared with the nonmixture model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / pharmacology
  • Clinical Trials, Phase III as Topic
  • Drug Administration Schedule
  • Female
  • Humans
  • Ipilimumab / administration & dosage*
  • Ipilimumab / pharmacology
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Models, Biological
  • Survival Analysis
  • Treatment Outcome
  • Tumor Burden / drug effects


  • Antineoplastic Agents, Immunological
  • Ipilimumab

Associated data