CPT: Pharmacometrics & Systems Pharmacology (Nov 2019)

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

  • Yan Feng,
  • Xiaoning Wang,
  • Satyendra Suryawanshi,
  • Akintunde Bello,
  • Amit Roy

DOI
https://doi.org/10.1002/psp4.12454
Journal volume & issue
Vol. 8, no. 11
pp. 825 – 834

Abstract

Read online

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.