目的：探讨PD-1抗体联合化疗对比抗血管生成药物联合化疗在晚期驱动基因阴性肺腺癌一线治疗中的疗效和安全性。方法：收集2018年3月至2021年8月河北医科大学第四医院收治的141例不可手术切除的ⅢB/ⅢC和Ⅳ期驱动基因阴性肺腺癌患者，回顾性分析PD-1抗体联合化疗对比抗血管生成药物联合化疗在一线治疗中的疗效与安全性。主要研究终点为无进展生存期（PFS），次要终点为客观缓解率（ORR）、疾病控制率（DCR）和不良反应。结果：141例患者均纳入生存分析，中位随访时间为13.0个月（95% CI：12.0～14.0）。PD-1抗体联合化疗组（A组）和抗血管生成药物联合化疗组（B组）的ORR分别为33.33%和27.38%，DCR分别为98.25%和89.29%，差异均无统计学意义。A组和B组的中位PFS分别为8.4个月（95% CI: 7.3～9.9）和6.9个月（95% CI: 6.1～7.7），差异无统计学意义。亚组分析结果显示，ⅢB/ⅢC期、肝或脑转移患者中，A组中位PFS较B组均延长（均P<0.01）。A组和B组不良反应发生率分别为26.32%和14.29%，多数为1~2级。结论：PD-1抗体联合化疗对比抗血管生成药物联合化疗一线治疗晚期驱动基因阴性肺腺癌疗效相当，不良反应可耐受，可成为晚期驱动基因阴性肺腺癌标准一线治疗。

Objective: To study the efficacy and safety of PD-1 antibody plus chemotherapy compared with those of antiangiogenic drug plus chemotherapy in the frontline treatment of advanced lung adenocarcinoma with negative driving genes. Methods: We collected data from 141 patients with unresectable stage ⅢB/ⅢC and Ⅳ lung adenocarcinoma with negative driving genes who were treated in the Fourth Hospital of Hebei Medical University from March 2018 to August 2021, and retrospectively studied the efficacy and safety of PD-1 antibody plus chemotherapy and those of antiangiogenic drug plus chemotherapy in frontline clinical application. The primary outcome measure was the progression-free survival (PFS), and the secondary outcome measures were objective response rate (ORR), disease control rate (DCR) and adverse reactions. Results: All of the 141 patients were included in the survival analysis. The median follow-up time was 13.0 months (95% CI: 12.0-14.0). The ORRs of PD-1 antibody plus chemotherapy group (group A) and antiangiogenic drug plus chemotherapy group (group B) were 33.33% and 27.38% respectively; the DCRs of group A and group B were 98.25% and 89.29%respectively, both with no statistical significance. The median PFSs of group A and group B were 8.4 months (95% CI: 7.3-9.9) and 6.9 months (95% CI: 6.1-7.7) respectively with no statistical significance. The results of subgroup analysis showed that the median PFSs of group A were longer than those of group B for stage ⅢB/ⅢC patients and patients with liver or brain metastasis (all P<0.01). The incidence of adverse reactions in group A and group B were 26.32% and 14.29% respectively, and most of the adverse reactions were grade 1-2. Conclusion: Compared with antiangiogenic drug plus chemotherapy, PD-1 antibody plus chemotherapy had the same efficacy in the frontline treatment of advanced lung adenocarcinoma with negative driving genes and the adverse reactions were tolerable. These two therapies could be standard first-line treatments for advanced lung adenocarcinoma with negative driving genes.

国家自然科学基金资助项目（No.81871894）