分析中药联合免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）治疗Ⅲ-Ⅳ期非小细胞肺癌（non-small cell lung cancer，NSCLC）的安全性，探讨 ICIs治疗Ⅲ-Ⅳ期 NSCLC发生免疫相关不良事件（immune-related adverse events，irAEs） 的影响因素。【方法】 回顾性分析2019年9月1日至2022年8月31日在广东省中医院大学城医院肿瘤科确诊为Ⅲ-Ⅳ期NSCLC 并接受中药联合ICIs治疗的住院患者的中医证型分布、相关用药信息以及irAEs发生情况等，并进行不良反应级别及可能的 影响因素分析。【结果】（1）90例NSCLC患者共涉及ICIs单药、ICIs联合化疗、ICIs联合抗血管生成药物、ICIs联合化疗及抗 血管生成药物4种治疗方案，其中以ICIs联合化疗及抗血管生成药物的治疗例数最多（52例，49.1%）；共使用8种不同的ICIs 药物，其中以替雷利珠单抗占比最高（43例，40.6%）。（2）将所有患者分为气虚痰瘀证、痰瘀阻络证、气阴两虚证、气血亏虚 证、痰热蕴结证5种证型，其中以气虚痰瘀证为最多（80例，88.9%）。（3）irAEs总体发生率为38.9%（35/90），其中发生G3及 以上irAEs的患者仅占5.6%（5/90）。初次发生irAEs的免疫治疗疗程主要集中在1～3程（17例，48.6%）。ICIs单药治疗的患者 出现G3及以上irAEs发生率高于联合治疗（33.3% vs 3.6%）。（4）美国东部肿瘤协作组的功能状态（performence status，PS）评分 为 0～1 分（OR=8.218，95%CI：1.607-42.023，P = 0.011）和有肾上腺转移（OR=4.497，95%CI：1.237-16.354，P = 0.022）是 ICIs治疗Ⅲ-Ⅳ期NSCLC发生irAEs的独立危险因素（均P＜0.05）。【结论】 中药有降低ICIs治疗Ⅲ-Ⅳ期NSCLC不良反应的潜 在可能；PS评分为0～1分和有肾上腺转移可能是ICIs治疗Ⅲ-Ⅳ期NSCLC发生irAEs的独立危险因素。

To investigate the clinical safety of Chinese medicine combined with immune checkpoint inhibitors （ICIs） for the treatment of non-small cell lung cancer （NSCLC） at stage Ⅲ-Ⅳ，and to explore the influencing factors of immune-related adverse events （irAEs） in the treatment of stage Ⅲ-Ⅳ NSCLC with ICIs. Methods A retrospective analysis was carried out for the investigation of the distribution of traditional Chinese medicine （TCM） syndromes， related medication information and the occurrence of irAEs in the hospitalized patients diagnosed as stage Ⅲ-Ⅳ NSCLC and treated with Chinese medicine combined with ICIs in the Oncology Department of Guangdong Provincial Hospital of Chinese Medicine （University-town Branch） from September 1， 2019 to August 31，2022. And the levels of adverse reactions and their possible influencing factors were analyzed. Results （1）The treatment for the 90 NSCLC patients involved 4 regimens， namely ICIs monotherapy， ICIs combined with chemotherapy，ICIs combined with anti-angiogenic drugs，and ICIs combined with chemotherapy and anti-angiogenic drugs. Among them，ICIs combined with chemotherapy and anti-angiogenic drugs were used most frequently for 52 cases（49.1%）. A total of 8 kinds of ICIs drugs were used，of which Tislelizumab accounted for the highest proportion（43 cases，40.6%）.（2）All of the patients were classified into 5 syndrome types，namely qi deficiency and phlegm-stasis syndrome， phlegm-stasis obstructing the collateral syndrome， qi and yin deficiency syndrome，qi and blood deficiency syndrome，and phlegm-heat accumulation syndrome. Among them， qi deficiency and phlegm-stasis syndrome was the most common type（80 cases， 88.9%）.（3）The overall incidence of irAEs was 38.9%（35/90），and irAEs being or above grade 3（G3） level in the patients only accounted for 5.6%（5/90）. The initial irAEs usually occurred at the immunotherapy course 1-3（17 cases，48.6%）. The incidence of irAEs being or above G3 level in the patients treated with ICIs monotherapy was higher than that in the patients treated with the combined therapy （33.3% vs 3.6%）.（4）The Eastern Cooperative Oncology Group（ECOG） performance status （PS） score of 0-1（OR=8.218，95%CI：1.607-42.023，P = 0.011） and adrenal metastasis （OR=4.497，95%CI：1.237-16.354，P=0.022） were the independent risk factors for irAEs in patients with stage Ⅲ-Ⅳ NSCLC treated by ICIs（P＜0.05）. Conclusion Chinese medicine has the potential to reduce the incidnence of adverse reactions of ICIs in the treatment of stage Ⅲ-Ⅳ NSCLC. PS score of 0-1 and adrenal metastasis may be the independent risk factors for irAEs in patients with stage Ⅲ-Ⅳ NSCLC treated by ICIs.

R273.342

广州市科学技术局重点研发项目（编号：202206010039）