Parameterization of a disease progression simulation model for sequentially treated metastatic human epidermal growth factor receptor 2 positive breast cancer patients

Abstract

Background The objective of this study is twofold: 1) to propose a simulation model for HER2+ metastatic breast cancer (mBC) which could further be used to assess the overall cost-effectiveness of the treatment sequences that would maximize survival of patients, and 2) to estimate transitional probabilities between treatment lines required to parameterize the simulation model, in the absence of individual patient data (IPD).

Methods Individual patient data (IPD) were reconstructed for treatment lines composing four treatment sequences. Parametric models were tested to select the model that best fits the IPD. The transitional probability equations, used for disease progression modeling, were obtained by substituting the parameters of the general equation for transitional probabilities by the parameters estimated from fitted distributions.

Results The log-logistic model best fitted the reconstructed data for progression-free and overall survival curves for each line of treatment. The shapes and scales of the log-logistic models were used to develop the transitional probability equations for the HER2+ mBC simulation model.

Key limitations: The estimation of the transitional probabilities depends heavily on the accuracy of the IPD reconstruction. Nonetheless, analytical and graphical tests can be performed to check the face validity of the reconstructed data. Additionally, sensitivity analyses can be conducted to test the impact of uncertainty surrounding the estimated parameters defining equations for transitional probabilities.

Conclusion The results of this study can be used as input in model-based economic evaluations of sequential therapy for HER2+ mBC.

Keywords:

• Disease progression modeling
• HER2-positive metastatic breast cancer
• Individual patient data reconstruction
• Sequential therapy
• Transitional probabilities

Declaration of funding

There was no commercial funding for this study. V.D. is supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number G12MD007582. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. GA. .is supported by the Virginia Commonwealth University/Massey Cancer Center (National Cancer Institute Grant # 5R25CA093423-09) Training Program in Cancer Prevention and Control Research. The publication of study results was not contingent on sponsor’s approval or censorship of the manuscript.

Declaration of financial/other relationships

V.D., A.A.A., G.A., C.G.K., and A.J.M. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Ellen Campbell PhD, Associate Professor and Director of the Division of Economic, Social and Administrative Pharmacy (ESAP) at the College of Pharmacy and Pharmaceutical Sciences (COPPS) at Florida A&M University, for her insightful comments on earlier versions of the paper.