Impact of chronic obstructive pulmonary disease on the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy for resectable non-small cell lung cancer: a retrospective cohort study

Abstract

Background Neoadjuvant immune checkpoint inhibitors(ICIs) combined with chemotherapy can improve non-small cell lung cancer(NSCLC) patients' pathological responses and show promising improvements in survival. Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease, and its associated abnormal inflammatory response affects not only the immunotherapy efficacy but also immune-related adverse events. It remains unclear whether NSCLC patients with COPD can benefit from neoadjuvant ICIs combined with chemotherapy. Methods A retrospective observational clinical study was conducted on 105 consecutive NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy at the Department of Thoracic Surgery of Tianjin Chest Hospital between April 2020 and April 2023. Results A total of 74 NSCLC patients were included in the study, including 30 patients with COPD and 44 patients without COPD. The percentage of patients with a pathological complete response (PCR) was higher in the COPD group than in the non-COPD group (43.3% vs. 20.5%, P = 0.042). Multivariate logistic regression analysis of factors associated with PCR showed that the adjusted odds ratio (OR) was statistically significant for presence of COPD (OR = 3.020, 95%CI: 1.042–8.757; P = 0.042). Major pathological response (66.7% vs. 50%, P = 0.155), R0 resection rate (96.7% vs.93.2%, P = 0.642), N2 lymph node downstaging(92.3% vs. 66.7%, P = 0.182) and objective response rate (70% vs. 63.6%, P = 0.57) were not significantly different between the groups. Progression-free survival(PFS) was not reached in the COPD group and 17 months (95%CI: 12.1–21.9) in the non-COPD group, with statistically significance (χ2 = 6.247, P = 0.012). Multivariate Cox’s regression analysis showed that the adjusted hazard ratio (HRadj) was statistically significant for presence of COPD (HRadj = 0.321, 95%CI: 0.111–0.930; P = 0.036). The grade 3 and grade 4 adverse events in the COPD group were leukopenia (3.3%, 6.7%), neutropenia (3.3%, 6.7%), fatigue (6.7%, 0%), gastrointestinal reactions (3.3%, 0%), and hypothyroidism (3.3%, 0%). In the non-COPD group, the corresponding adverse events were leukopenia (6.8%, 6.8%), neutropenia (3.3%, 6.8%), fatigue (2.3%, 0%), gastrointestinal reactions (2.3%, 0%), and hypothyroidism (2.3%, 0%), respectively. Conclusions The present study indicates that the presence of COPD may improve PCR, prolong PFS, and have an acceptable safety profile in NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy.

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

“…Consequently, ever-growing attention has been paid to this cohort, leading to special recommendations by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) that guide clinicians on the management of patients with COPD, stating that concomitant chronic diseases, including lung cancer, should be actively sought and appropriately treated as they can independently influence both mortality and hospitalisations [120]. Several studies that investigated patients affected by NSCLC and a moderate-to-severe COPD comorbidity showed prolonged PFS and OS [5,7,68,121,122] and higher ORR [101,123] when compared to patients without COPD, and better survival and responses were also observed in patients with only mild COPD [124] (Table 3). Notable, despite OS not significantly differing between COPD and non-COPD patients, it became significant when the patients were stratified for smoking status (being higher in current smokers than in previous smokers) [5,6,68,123].…”