Tumor growth inhibition-overall survival modeling in non-small cell lung cancer: A case study from GEMSTONE-302

Abstract

Overall survival is vital for approving new anticancer drugs but is often impractical for early-phase studies. The tumor growth inhibition-overall survival (TGI-OS) model could bridge the gap between early- and late-stage development. This study aimed to identify an appropriate TGI-OS model for patients with non-small cell lung cancer from the GEMSTONE-302 study of sugemalimab. We used three TGI models to delineate tumor trajectories and investigated three OS model for linking TGI metric to OS. All three TGI models accurately captured tumor profiles at the individual level. The published atezolizumab-based TGI-OS model predicted survival time satisfactorily through simulation-based evaluation, whereas the other published model built from multi-treatment underestimated OS. Our study-specific TGI-OS model identified time-to-growth as the most significant metric with the number of metastatic sites and neutrophil-to-lymphocyte ratio at baseline as covariates and exhibited robust OS predictability. Our findings demonstrated the effectiveness of the TGI-OS models in predicting phase III outcomes, which underpins their value as a powerful tool for antitumor drug development.

FIGURE 1

Individual predicted versus observed tumor sizes (sum of the longest diameters) from three tumor‐growth‐inhibition models. The red dashed lines represent unity and the blue solid lines represent linear smooth.

FIGURE 2

The time course of tumor size (sum of the longest diameters) from observation and prediction for representative (the first and last 10) patients in the GEMSTONE‐302 study. The dots represent observations, and the red, blue, and green lines represent the individual predictions from Wang's, Stein's, and Claret's tumor‐growth‐inhibition models, respectively.

FIGURE 3

Prediction of OS distribution in the GEMSTONE‐302 study from Wang's, Chan's, and study‐specific TGI‐OS models. Solid line represents the observed Kaplan–Meier curve whereas the vertical lines mark censored observations. The shaded area represents the 95% confidence interval spread of the 2.5th to 97.5th percentiles of predicted values from 1000 simulations; green: sugemalimab plus chemotherapy, red: placebo plus chemotherapy. TGI‐OS, tumor growth inhibition‐overall survival.