COPD patients with non-small cell lung cancer respond better to anti-PD-(L)1 immune checkpoint inhibitors

In studies evaluating the efficacy of anti-programmed cell death 1/ligand 1 immune checkpoint inhibitors (anti-PD-(L)1) among patients with non-small cell lung cancer (NSCLC), smokers tend to have better clinical outcomes than non-smokers. However, it is unclear whether NSCLC patients with co-existing chronic obstructive pulmonary disease (COPD) have better clinical outcomes than patients without COPD, regardless of smoking history. The potential correlation of COPD with an improved response to anti-PD-(L)1 was examined in a large cohort of patients with available pulmonary function test results. Patients with stage IV NSCLC who received a minimum of two doses of anti-PD-(L)1 across various treatment lines from 2015 to 2021 were enrolled. Among the 387 patients, pulmonary function test (PFT) data were available for 234 (61%), 139 (59%) of whom had spirometry diagnosed COPD. A retrospective analysis was conducted to evaluate overall survival (OS) and progression-free survival (PFS) based on the presence or absence of COPD. In the univariate analyses, both PFS and OS significantly improved among patients with COPD, compared with patients who did not have COPD (HR 0.71, 95% CI 0.56-0.89 for PFS; HR 0.69, 95% CI 0.52-0.92 for OS), regardless of smoking status. In the multivariate analyses, PFS and OS remained superior among patients with COPD (HR 0.66, 95% CI 0.51-0.85 for PFS; HR 0.63, 95% CI 0.47-0.85 for OS). Additionally, patients with milder COPD (GOLD 1/2 vs. 3/4) had better clinical outcomes than patients with more severe disease. However, neither lung distension (defined as a total lung capacity > 120%) nor pre-COPD status (defined as a diffusing capacity of lung for carbon monoxide < 70%) had a significant impact on PFS or OS. Our study, conducted in the largest cohort with available PFT data to date, showed that COPD was associated with improved survival outcomes among patients with stage IV NSCLC who received anti-PD-(L)1 treatment, regardless of smoking history. The differences were mainly driven by mild and moderate obstruction (GOLD 1 and 2). The dysregulated PD-1/PD-L1 expression that occurs in COPD may offer insights into the different outcomes and thus warrants further investigation.