Abstract:

Objective　To evaluate the efficacy and safety of recombinant human endostatin injection combined with immune checkpoint inhibitors (ICIs) in the first-line treatment of non-small cell lung cancer (NSCLC). Methods　A retrospective analysis was performed on 484 patients with unresectable NSCLC who received at least 4 cycles of anti-tumor therapy in Yuebei People's Hospital from January 2020 to January 2022, and they were divided into 3 groups according to the treatment methods. Among the 85 cases of the E+ICI group, there were 58 males and 27 females, aged 68 (61, 76) years, and they were treated with recombinant human endostatin injection +ICIs. Recombinant human endostatin injection was injected 210 mg each time with continuous chemotherapy pump for 3 d, once every 3 weeks; ICIs were used according to the operating instructions; recombinant human endostatin injection and ICIs did not allow dose reduction. Among the 351 cases of the C+ICI group, there were 256 males and 95 females, aged 61 (51, 70) years, and they were treated with chemotherapy +ICIs. The chemotherapy drugs included carboplatin (AUC=5) or cisplatin 75 mg/m², gemcitabine 1 g/m², docetaxel 75 mg/m², and pemetrexed 500 mg/m² or paclitaxel 175 mg/m². The dose of chemotherapy drugs was adjusted according to clinical routine, and the patients with less than 75% standard dose were excluded. Among the 48 cases of the ICI group, there were 37 males and 11 females, aged 72 (68, 78) years, and they received ICIs monotherapy. After 4 to 6 cycles of palliative treatment, the E+ICI group was given maintenance treatment with the same dose of recombinant human endostatin injection and ICIs, and the C+ICI group and ICI group were given ICI maintenance treatment once a month until the disease progressed or the intolerant toxicity occurred. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were objective response rate (ORR) and PFS and OS in the elderly subgroup. χ² test, Kruskal-Wallis H test, and Log-rank test were used. Results　The PFS (mPFS: 8.12 months vs. 8.96 months, P=0.131) and OS (mOS: 16.32 months vs. 17.28 months, P=0.160) of the E+ICI group and C+ICI group were similar. The PFS and OS of the E+ICI group were superior to those of the ICI group (mPFS: 8.12 months vs. 6.16 months, P=0.009; mOS: 16.32 months vs. 10.10 months, P=0.001). The ORRs of the E+ICI group, C+ICI group, and ICI group were 52.94%, 48.43%, and 35.42%, respectively, with no statistically significant difference (P=0.142). The incidence of treatment-related adverse events (AEs) above grade 3 in the E+ICI group was lower than that in the C+ICI group. There were 41 cases ≥70 years old in the E+ICI group, 111 cases in the C+ICI group, and 27 cases in the ICI group, respectively. Among the elderly patients (≥70 years old), the mPFS and mOS in the E+ICI group were higher than those in the ICI group (10.08 months vs. 6.16 months, P=0.003; 16.68 months vs. 10.03 months, P<0.001). Conclusion　Recombinant human endostatin injection combined with ICIs is well tolerated in the treatment of NSCLC, and its efficacy is comparable to that of chemotherapy combined with ICIs, but superior to ICIs monotherapy.

Key words:

Non-small cell lung cancer, Recombinant human endostatin, Immune checkpoint inhibitors, Real-world study

摘要：

目的　本研究旨在评估重组人血管内皮抑制素注射液联合免疫检查点抑制剂（ICIs）一线治疗非小细胞肺癌（NSCLC）的疗效和安全性。方法　回顾性分析粤北人民医院2020年1月至2022年1月接受至少4个周期抗肿瘤治疗的不可切除NSCLC患者484例，按治疗方法分为3组。E+ICI组85例中男58例、女27例，年龄68（61，76）岁，接受重组人血管内皮抑制素注射液+ICIs治疗，重组人血管内皮抑制素注射液每次210 mg持续化疗泵输注维持3 d，每3周注射1次；ICIs的使用参照说明书；重组人血管内皮抑制素注射液和ICIs不允许降低剂量。C+ICIs组351例中男256例、女95例，年龄61（51，70）岁，接受化疗+ICIs治疗，化疗药物包括卡铂（AUC=5）或顺铂75 mg/m²，吉西他滨1 g/m²，多西他赛75 mg/m²，培美曲塞500 mg/m²或紫杉醇175 mg/m²，根据临床常规对化疗药物进行剂量调整，排除低于75%标准剂量患者。ICI组48例中男37例、女11例，年龄72（68，78）岁，接受ICIs单药治疗。4～6个周期姑息治疗后，E+ICI组以相同剂量重组人血管内皮抑制素注射液及ICIs维持治疗，C+ICI组和ICI组以ICIs维持治疗，每个月注射1次直至疾病进展或出现不耐受毒性反应。主要研究终点是无进展生存期（PFS）和总生存期（OS），次要研究终点是客观缓解率（ORR）和高龄亚组的PFS和OS。采用χ²检验、Kruskal-Wallis H检验、Log-rank检验。结果　E+ICI组与C+ICI组具有相似的PFS（mPFS：8.12个月比8.96个月，P=0.131）和OS（mOS：16.32个月比17.28个月，P=0.160），E+ICI组的PFS、OS均长于ICI组（mPFS：8.12个月比6.16个月，P=0.009；mOS：16.32个月比10.10个月，P=0.001）。E+ICI组、C+ICI组和ICI组的ORR分别为52.94%、48.43%、35.42%，差异无统计学意义（P=0.142）。E+ICI组3级以上治疗相关不良事件（AEs）发生率低于C+ICI组。E+ICI组、C+ICI组、ICI组就诊时年龄≥70岁患者分别有41例、111例、27例。在高龄（≥70岁）患者中，E+ICI组的mPFS、mOS均长于ICI组（10.08个月比6.16个月，P=0.003；16.68个月比10.03个月，P<0.001）。结论　重组人血管内皮抑制素注射液联合ICIs治疗NSCLC耐受性良好，疗效与化疗联合ICIs治疗相当，但优于ICIs单药治疗。

关键词:

非小细胞肺癌, 重组人血管内皮抑制素, 免疫检查点抑制剂, 真实世界研究