Obesity and survival in advanced non-small cell lung cancer patients treated with chemotherapy, immunotherapy, or chemoimmunotherapy: a multicenter cohort study

Abstract

Background: The association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study.

Methods: We retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan-Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios.

Results: In the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76-0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82-1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64-0.84), but no association observed in women (HR = 0.96, 95% CI 0.81-1.13, P_{interaction =} 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores.

Conclusions: Obesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.

Keywords: Body mass index; Non-small cell lung cancer; Obesity; Survival.

Fig. 1

Progression-free survival and overall survival by BMI category. Progression-free survival in patients in the A CGDB-Chemo cohort, B CGDB-Immu cohort, C CGDB-Chemoimmu cohort. Overall survival in patients in the D CGDB-Chemo cohort, E CGDB-Immu cohort, F CGDB-Chemoimmu cohort

Fig. 2

Overall survival by BMI category and sex. Overall survival in male patients in the A CGDB-Chemo cohort, B CGDB-Immu cohort, C CGDB-Chemoimmu cohort. Overall survival in female patients in the D CGDB-Chemo cohort, E CGDB-Immu cohort, F CGDB-Chemoimmu cohort

Fig. 3

Progression-free survival by BMI category and sex. Progression-free survival in male patients in the A CGDB-Chemo cohort, B CGDB-Immu cohort, C CGDB-Chemoimmu cohort. Progression-free survival in female patients in the D CGDB-Chemo cohort, E CGDB-Immu cohort, F CGDB-Chemoimmu cohort

Fig. 4

Pooled analysis. Forest plots of average adjusted hazard ratios (HRs) for patients with obese BMI compared with normal BMI by treatment type and sex for progression-free survival and overall survival

Fig. 5

The level of biomarker by BMI category. Association between BMI and A tissue tumor mutational burden and B PD-L1 expression in CGDB cohorts. Association between BMI and C ESTIMATE score, D ESTIMATE Immune Score, and E ESTIMATE Stromal Score