Cure Rate Joint Model for Time-to-Event Data and Longitudinal Tumor Burden with Potential Change Points

TL;DR

This paper introduces a joint modeling approach for time-to-event and longitudinal tumor burden data in NSCLC, incorporating change points to better capture disease progression and treatment effects.

Contribution

A novel joint model that estimates individualized change points in tumor burden, improving analysis of disease progression in clinical trials.

Findings

Model outperforms traditional methods in simulations

Prolonged tumor burden reduction observed in treatment group

Robust estimates of disease progression patterns

Abstract

In non-small cell lung cancer (NSCLC) clinical trials, tumor burden (TB) is a key longitudinal biomarker for assessing treatment effects. Typically, standard-of-care (SOC) therapies and some novel interventions initially decrease TB; however, many patients subsequently experience an increase-indicating disease progression-while others show a continuous decline. In patients with an eventual TB increase, the change point marks the onset of progression and must occur before the time of the event. To capture these distinct dynamics, we propose a novel joint model that integrates time-to-event and longitudinal TB data, classifying patients into a change-point group or a stable group. For the change-point group, our approach flexibly estimates an individualized change point by leveraging time-to-event information. We use a Monte Carlo Expectation-Maximization (MCEM) algorithm for efficient parameter estimation. Simulation studies demonstrate that our model outperforms traditional approaches by accurately capturing diverse disease progression patterns and handling censoring complexities, leading to robust marginal TB outcome estimates. When applied to a Phase 3 NSCLC trial comparing cemiplimab monotherapy to SOC, the treatment group shows prolonged TB reduction and consistently lower TB over time, highlighting the clinical utility of our approach. The implementation code is publicly available on https://github.com/quyixiang/JoCuR.