ABSTRACT Programmed cell death (PD) protein (ligand L)‐1 inhibitors are established treatments for metastatic non‐small cell lung cancer (mNSCLC). In oncology, progression‐free survival (PFS) and objective response rate (ORR) are often used as surrogates for overall survival (OS) to inform clinical development; however, there remains uncertainty in the concordance between these endpoints. This study evaluated the impact of a broad set of PD‐(L)1 inhibitors on efficacy, explored the relationship between ORR and survival endpoints, and compared PD‐1 and PD‐L1 treatments for mNSCLC. A dataset of 114 studies was used to conduct a sequential two‐stage model‐based meta‐analysis (MBMA). Firstly, an MBMA with mixed‐effects logistic regression was applied to evaluate treatment‐specific and clinical covariate effects on ORR. Secondly, MBMAs for OS and PFS were conducted with a mixed‐effects semi‐parametric proportional hazard approach using digitized Kaplan–Meier curves, with the treatment type, covariates, and ORR as inputs. ORR was demonstrated to be a significant predictor of OS and PFS. Simulations of head‐to‐head comparisons of treatment types were conducted using these models. Trends in predicted outcomes numerically favored PD‐1 over PD‐L1 treatments, but differences were not statistically significant. These findings support evidence‐based decision‐making for late‐stage trial designs using ORR data from earlier phase trials, enabling benchmarking of emerging data by adjusting for explained and unexplained sources of variability in existing and emerging data.
Franzese et al. (Wed,) studied this question.