Model-Based Meta-Analysis of Overall Survival in Vulnerable Platinum-Ineligible NSCLC Populations

IPSOS (NCT03191786) is a Phase III trial comparing atezolizumab (atezo) monotherapy to single-agent chemotherapy (gemcitabine or vinorelbine) in patients with treatment-naïve locally advanced or metastatic NSCLC unsuitable for platinum-doublet chemotherapy. The study demonstrated significant overall survival (OS) improvement in the atezo arm compared to single-agent chemotherapy, with a stratified hazard ratio (HR) of 0.78 (95% CI: 0.63-0.97; p = 0.028). Since the IPSOS control arm only allowed gemcitabine or vinorelbine, a model-based meta-analysis (MBMA) was conducted, extracting OS data from published literature in similar patients, adjusting for population differences across trials, to estimate the HR between IPSOS arms versus historical trials which utilized single-agent chemotherapies. The aim was to demonstrate the non-inferiority of the IPSOS control arm versus historical controls. The literature search included patients who were chemotherapy-naïve, had advanced or metastatic NSCLC, were platinum-ineligible, ≥ 70 years or had ECOG ≥ 2, and were treated with single-agent paclitaxel, docetaxel, gemcitabine, pemetrexed, or vinorelbine. Summary-level OS data were extracted by digitizing Kaplan-Meier curves, resulting in a database of 26 trials with 41 arms and 3637 participants. A nonparametric approach modeling the conditional probability of OS data was implemented. After adjusting for ECOG PS (the only significant covariate), the model-predicted HR for the IPSOS control arm relative to historical trials was 0.543 (95% CI: 0.435-0.677), and the HR for the IPSOS atezo monotherapy arm was 0.418 (95% CI: 0.335-0.522). Overall, the MBMA results support the benefit of atezo seen in the IPSOS trial.