COPD patients with NSCLC respond better to immune checkpoints inhibitors

Introduction: COPD patients with Non-Small Cell Lung Cancer (NSCLC) have better clinical outcomes with Immune Checkpoint Inhibitors (ICI) than non-COPD, independently of tobacco consumption. However, the COPD classification criteria was composite in most studies, with few available Pulmonary Function Tests (PFT). The aim of this study was to reinforce the evidence of a link between COPD and ICI with a larger PFT-available cohort and to evaluate if COPD function characteristics have any effect on ICI clinical outcomes. Methods: Between 2015 and 2021, 387 patients who received at least two doses of an anti-programmed cell death 1 (PD-1)/ ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) at any treatment line for a stage IV NSCLC were included in Bordeaux; 279 had available PFT and 169 were diagnosed COPD. Overall survival (OS) and progression-free survival (PFS) were analyzed according to the presence of COPD. Results: In univariate analyses PFS and OS were significantly better among subjects with COPD (respectively HR 0.76, 95% CI 0.62-0.93 and HR 0.74, 95% CI 0.60-0.91). In the multivariate analysis, PFS and OS remained better in the COPD population (respectively HR 0.74, 95% CI 0.59-0.92 and HR 0.74, 95% CI 0.59-0.91). Milder COPD had better clinical outcomes than the more severe ones. Lung hyperinflation (defined by TLC>120%) and pre-COPD status (defined by DLCO<70%) had no impact on PFS or OS. Conclusion: This is the largest existing cohort showing that COPD is associated with a better survival in stage IV NSCLC treated with ICI, independently of tobacco, especially in milder COPD. Dysregulation of the expression of PD-1/PD-L1 in COPD patients might explain these differences and should be better explored.