Subgroup identification of targeted therapy effects on biomarker for time to event data.

BACKGROUND

The initiation biomarker-driven trials have revolutionized oncology drug development by challenging the traditional phased approach and introducing basket studies. Notable successes in non-small cell lung cancer (NSCLC) with ALK, ALK/ROS1, and EGFR inhibitors have prompted the need to expand this approach to other cancer sites.

OBJECTIVES

This study explores the use of dose response modeling and time-to-event algorithms on the biomarker molecular targeted agent (MTA). By simulating subgroup identification in MTA-related time-to-event data, the study aims to develop statistical methodology supporting biomarker-driven trials in oncology.

METHODS

A total of n patients are selected assigned for different doses. A dataset is prepared to mimic the situation on Subgroup Identification of MTA for time to event data analysis. The response is measured through MTA. The MTA value is also measured through ROC. The Markov Chain Monte Carlo (MCMC) techniques are prepared to perform the proposed algorithm. The analysis is carried out with a simulation study. The subset selection is performed through the Threshold Limit Value (TLV) by the Bayesian approach.

RESULTS

The MTA is observed with range 12-16. It is expected that there is a marginal level shift of the MTA from pre to post-treatment. The Cox time-varying model can be adopted further as causal-effect relation to establishing the MTA on prolonging the survival duration. The proposed work in the statistical methodology to support the biomarker-driven trial for oncology research.

CONCLUSION

This study extends the application of biomarker-driven trials beyond NSCLC, opening possibilities for implementation in other cancer sites. By demonstrating the feasibility and efficacy of utilizing MTA as a biomarker, the research lays the foundation for refining and validating biomarker use in clinical trials. These advancements aim to enhance the precision and effectiveness of cancer treatments, ultimately benefiting patients.