Department of Respiratory and Critica Care Medicine, Tianjin Chest Hospital, Affiliated Chest Hospital of Tianjin University, Tianjin, China.
Department of Thoracic Surgery, Tianjin Chest Hospital, Affiliated Chest Hospital of Tianjin University, Tianjin, China.
BMC Cancer. 2024 Jan 30;24(1):153. doi: 10.1186/s12885-024-11902-w.
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.
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.
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 (χ = 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.
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.
新辅助免疫检查点抑制剂（ICIs）联合化疗可以提高非小细胞肺癌（NSCLC）患者的病理反应，并在生存方面显示出有希望的改善。慢性阻塞性肺疾病（COPD）是一种系统性炎症性疾病，其相关的异常炎症反应不仅影响免疫治疗的疗效，还影响免疫相关不良事件。目前尚不清楚是否 NSCLC 合并 COPD 患者可以从新辅助 ICIs 联合化疗中获益。
回顾性观察性临床研究，纳入 2020 年 4 月至 2023 年 4 月在天津市胸科医院胸外科接受新辅助 ICIs 联合化疗的 105 例 NSCLC 患者。
共有 74 例 NSCLC 患者纳入研究，其中 COPD 组 30 例，非 COPD 组 44 例。COPD 组病理完全缓解（PCR）率高于非 COPD 组（43.3%比 20.5%，P=0.042）。多因素逻辑回归分析 PCR 相关因素显示，COPD 存在的调整后比值比（OR）有统计学意义（OR=3.020，95%CI：1.042-8.757；P=0.042）。主要病理反应（66.7%比 50%，P=0.155）、R0 切除率（96.7%比 93.2%，P=0.642）、N2 淋巴结降期（92.3%比 66.7%，P=0.182）和客观缓解率（70%比 63.6%，P=0.57）在两组间无显著差异。COPD 组无进展生存期（PFS）未达到，非 COPD 组为 17 个月（95%CI：12.1-21.9），有统计学意义（χ2=6.247，P=0.012）。多因素 Cox 回归分析显示，COPD 存在的调整后风险比（HRadj）有统计学意义（HRadj=0.321，95%CI：0.111-0.930；P=0.036）。COPD 组的 3 级和 4 级不良事件为白细胞减少（3.3%，6.7%）、中性粒细胞减少（3.3%，6.7%）、疲劳（6.7%，0%）、胃肠道反应（3.3%，0%）和甲状腺功能减退（3.3%，0%）。非 COPD 组相应的不良事件为白细胞减少（6.8%，6.8%）、中性粒细胞减少（3.3%，6.8%）、疲劳（2.3%，0%）、胃肠道反应（2.3%，0%）和甲状腺功能减退（2.3%，0%）。
本研究表明，在接受新辅助 ICIs 联合化疗的 NSCLC 患者中，COPD 的存在可能提高 PCR、延长 PFS，并具有可接受的安全性。
