The impact of obesity on survival in non-small cell lung cancer patients receiving immune checkpoint inhibitor therapy: A retrospective multi-institutional US cohort study.

Abstract

e20630 Background: Immune checkpoint inhibitor (ICI) therapy is a cornerstone in the treatment of metastatic non-small cell lung cancer (NSCLC). However, many patients develop resistance or fail to respond to ICI. There has been a lot of interest in studying the host factors that might influence the response to immunotherapy. In recent years, the Obesity paradox phenomenon has been studied in multiple cancers. However, there is scarce information on the impact of obesity on the various ICI therapies on NSCLC patients in the US. In this study, we are presenting the first real-world analysis of the effect of obesity on survival in US based patients diagnosed with metastatic NSCLC and receiving ICIs. We also tried to unveil any possible underlying mechanisms that might explain this phenomenon like complications and immune‐related adverse events (irAEs). Methods: Data was retrospectively collected from the independent US population-based TriNetX network, a national electronic health record database with 120 million US patients from over 70 healthcare organizations. We identified patients ≥ 18 years old with non-small cell lung cancer diagnosis who received ICI therapy between 2012 and 2024. ICI therapies included pembrolizumab, nivolumab, atezolizumab, durvalumab, ipilimumab and cemiplimab. Patients were then split into two cohorts: those with normal BMI (18.5-24.9) and obese BMI (≥30). Patients were then 1:1 propensity score matched based on age, sex, race, ethnicity, type of ICI therapy used, comorbidities and staging. Overall survival (OS), NSCLC related complications and irAEs were measured at 6 months, 1 year and 3 years after initiation of ICI treatment. Results: We identified 10,056 patients over the age of 18 who received ICI therapy for NSCLC. After 1:1 matching, each cohort in our analysis included 2762 patients. In the normal and obese groups mean age in both groups was 66.2 ± 10.8 and 66.3 ± 9.69 years respectively. Patients were also more likely to be white (73%) and male (49%) in both groups. Obesity BMI was associated with significantly improved OS at 6 months (hazard ratio [HR], 0.78 [95% CI, 0.66-0.83]), 1 year (HR, 0.81 [95% CI, 0.74-0.89]), and 3 years (HR, 0.88 [95% CI, 0.81-0.95]) after ICI treatment, compared with patients with normal BMI. There was no difference in rates of NSCLC specific complications or irAEs at any of the time points from 6 months to 3 years. Conclusions: Analysis of one of the largest US based databases showed that obesity is associated with better overall survival without significant difference in complications or irAEs which suggest that the difference in the survival is likely due to the direct effect of the obesity on the cancers. Further clinical trials and transitional studies should be geared towards investigating the effects of obesity on tumor microenvironment.