The following is the summary of “Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit” published in the December 2022 issue of Thoracic oncology by Lin, et al.


It is unclear if treatment with immune checkpoint inhibitors (ICIs) improves survival rates in lung cancer.  Researchers searched the PubMed database up to and including February 14, 2022, for randomized controlled trials of ICI in lung cancer, and investigators assessed the discovered publications for eligibility. Cox hazard ratios (HRs) were adjusted to Cox-TEL HRs for ICI short-term survivors (ST-HRs) and differences in proportions for patients with long-term survival based on published data on overall survival (LT-DP). The meta-analyses were conducted with a frequentist random-effects model. Stratified by programmed death-ligand 1 (PD-L1) level (primary outcome) and ICI treatment line, the pooled overall survival Cox HR, ST-HR, and LT-DP in NSCLC were of interest (secondary).

In all, 9 studies from 8 different clinical trials were chosen for meta-analysis. Patients having PD-L1 expression of 1% or less, 1% to 50%, and 50% were categorized as follows by the primary analysis: Cox hazard ratios (all pooled): pooled Cox HR, 0.71 (95% CI: 0.62-0.82), 0.74 (95% CI: 0.68-0.82), and 0.62 (95% CI: 0.54-0.70); standardized mortality ratios (all pooled): 0.91 (95% CI: 0.79-1.05), 0.88 (95% CI: 0.82-0.94), and 0.70 (95% CI: 0.60-0.83); and pooled LT-DP, 0.10 (95% CI: 0.00–0.20), 0.09 (95% CI: 0.06–0.12), and 0.11 (95% CI: 0.05–0.17).LT hazard ratio. 

The secondary study showed that the LT-DP was roughly 10% between the 2 groups. This study shows that among PD-L1-positive subpopulations, long-term survivors of either ICI treatment line have a roughly 10% higher probability of survival compared to non-survivors. More so, ST-HR was consistently inferior to Cox HR. Neither LT-DP nor ST-HR reached statistical significance for patients with PD-L1 below 1%. The study sheds light on the effectiveness of ICI as a therapy in previously conducted studies.

Source: sciencedirect.com/science/article/abs/pii/S1556086422015520