Treatment response and safety of immunotherapy for advanced non-small cell lung cancer with comorbid chronic obstructive pulmonary disease: a retrospective cohort study

Abstract

Background: Immunotherapy has provided a novel therapeutic option for lung cancer but studies involving patients with advanced non-small cell lung cancer (NSCLC) coupled with various degrees of comorbid chronic obstructive pulmonary disease (COPD) are limited. Thus, we performed a retrospective cohort study to optimize the use of immunotherapy in this special population. Methods:We enrolled a total of 99 patients with advanced (stage IIIB/C-IV) NSCLC with comorbid COPD who had received immune checkpoint inhibitors (ICIs) according to the inclusion and exclusion criteria. They were divided into four groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline criteria as follows: no COPD group (n 1 =19), mild COPD group (n 2 =24), moderate COPD group (n 3 =31), and severe COPD group (n 4 =25). Routine blood, imaging characteristics, related cytokines including interleukin (IL)-6, IL-8, IL-10, etc., Krebs Von den Lungen (KL)-6, and corresponding indicators of immune-related adverse events (irAEs), incidence of irAEs, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were recorded and analyzed. Comparability of baseline factors above and clinical characteristics were evaluated.Results: There were statistically significant differences in the incidence of irAEs among the four groups (P=0.003). The incidence of irAEs in patients with no COPD (n 1 , 21.1%) and mild to moderate COPD (n 2/3 , 8.3%, 32.3%) was lower than that in patients with severe COPD (n 4 , 56.0%) (P=0.003). The median PFS of the mild to moderate COPD group was significantly longer than the severe COPD group (19.0 vs. 8.00 months, log-rank P=0.004). A significant increase of both ORR (P=0.004) and DCR (P=0.037), as well as higher IL-6 (P=0.000), IL-8 (P=0.026), and IL-10 (P=0.010) levels, have been observed in the mild to moderate COPD group compared with severe COPD group. IL-6 level was an independent factor influencing PFS [P=0.007, 95% confidence interval (95% CI): 1.000-1.002] and COPD grading was an independent predictor of irAEs (P=0.037, 95% CI: 1.035-3.039).Conclusions: Immunotherapy should be selected with caution for advanced NSCLC patients with comorbid severe COPD, considering the limited efficacy and the increased risk of immune-related adverse events related to the immune-checkpoint inhibitors administration in this special population.

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

“…Compared with neoadjuvant chemotherapy, neoadjuvant ICIs combined with chemotherapy can significantly improve the PCR, EFS, and overall survival of patients with NSCLC [ 8 , 9 , 21 , 22 ]. However, no studies focused on COPD, a common comorbidity of NSCLC, which may be related to the efficacy and toxicity of immune checkpoint inhibitors [ 13 – 17 ]. Our study investigated the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with NSCLC and COPD.…”

“…COPD is a systemic inflammatory disease, and its associated abnormal inflammatory response affects not only the immunotherapy efficacy but also immune-related adverse events (irAEs). Zhang et al found that the incidence of irAEs in patients with advanced NSCLC with COPD was associated with the GOLD grade, while the incidence in patients with mild-to-moderate COPD was similar to that in patients without COPD [ 17 ]. In the present study, we found that the types and rates of treatment-related adverse events were similar in both the COPD and non-COPD groups, suggesting that COPD does not increase the toxicity of neoadjuvant immunotherapy.…”

“…However, the immune microenvironments differ between early and advanced stages of lung cancer [ 10 ]. In addition, abnormal inflammatory responses in patients with COPD may increase treatment-related adverse reactions [ 17 ]. Thus, it remains unclear whether patients with NSCLC and COPD benefit from neoadjuvant ICIs treatment in combination with chemotherapy.…”

Cause of death among gastric cancer survivors in the United States from 2000 to 2020

“…[23] Meanwhile, immune-related adverse effects may lead to the incidence or exacerbation of infectious diseases, which are important contributors to COPD. [24] Physicians should pay closer attention to the particular comorbidities associated with the use of these anticancer therapies.…”

Elucidating the Prognostic Biomarkers and Immune Correlations in the Co- occurrence of Chronic Obstructive Pulmonary Disease and Lung Squamous Cell Carcinoma

“…According to a retrospective cohort study, it was found that immunotherapy should be selected with caution for advanced NSCLC patients with comorbid severe COPD. This is due to the limited e cacy of immunotherapy in this population and the increased risk of immune-related adverse events associated with the administration of immune checkpoint inhibitors [29].On the other hand, emerging immune pro ling data suggest that NSCLC patients with COPD may have a higher sensitivity to immune checkpoint inhibitors compared to those without COPD. This indicates that COPD may have a clinical impact on the treatment outcome of immunotherapy [30].…”