抗 PD-1/L1 联合抗血管生成治疗作为晚期肺腺癌二线或后线治疗。

Anti-PD-1/L1 plus anti-angiogenesis therapy as second-line or later treatment in advanced lung adenocarcinoma.

机构信息

School of Medicine, Nankai University, 94 Weijin Road, Nankai, Tianjin, 300071, People's Republic of China.

Department of Medical Oncology, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2021 Mar;147(3):881-891. doi: 10.1007/s00432-020-03380-x. Epub 2020 Sep 9.

DOI:10.1007/s00432-020-03380-x

PMID:32909095

Abstract

PURPOSE

Anti-programmed cell death protein 1 or its ligand (anti-PD-1/L1) monotherapy has become the standard second-line treatment in advanced lung adenocarcinoma. However, the strategy treatment of anti-PD-1/L1 plus anti-angiogenesis therapy has not been evaluated. We conducted this retrospective study to assess the efficacy and safety of anti-PD-1/L1 plus anti-angiogenesis therapy in patients with advanced lung adenocarcinoma in the second-line or later setting.

METHODS

Patients with advanced lung adenocarcinoma who received anti-PD-1/L1 plus anti-angiogenesis therapy or anti-PD-1/L1 monotherapy in the second-line or later treatment from March 2015 to May 2019 in PLA General Hospital were retrospectively analyzed. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Multivariate analyses of PFS and OS were performed with Cox proportional hazard regression models.

RESULTS

Seventy-four patients were included in our study. Twenty-five patients were treated with anti-PD-1/L1 plus anti-angiogenesis therapy, and forty-nine patients were treated with anti-PD-1/L1 monotherapy. The disease control rate (DCR) was higher in the anti-PD-1/L1 plus anti-angiogenesis group than in the anti-PD-1/L1 monotherapy group (92.0% vs. 46.9%, P = 0.0004). The median progression-free survival (PFS) was 5.1 months vs. 2.0 months (HR 0.551 [95% confidence interval 0.337-0.902], P = 0.002) and median overall survival (OS) was 14.3 months vs. 8.4 months (HR 0.549 [95% CI 0.305-0.990], P = 0.046), respectively. Multivariate Cox proportional hazard regression models showed that anti-PD-1/L1 plus anti-angiogenesis group had prolonged PFS (HR 0.541 [95% CI 0.298-0.981], P = 0.033). The incidences of grade 3/4 adverse events were 12% (3/25) in anti-PD-1/L1 plus anti-angiogenesis group and 6% (3/49) in anti-PD-1/L1 monotherapy group.

CONCLUSION

Compared with anti-PD-1/L1 monotherapy, anti-PD-1/L1 plus anti-angiogenesis therapy could significantly improve the clinical response and bring longer PFS and OS in patients with advanced lung adenocarcinoma who had failed first-line or later treatment. Further prospective studies are needed to validate our findings.

摘要

目的

抗程序性细胞死亡蛋白 1 或其配体（抗 PD-1/L1）单药治疗已成为晚期肺腺癌二线治疗的标准方案。然而，抗 PD-1/L1 联合抗血管生成治疗的策略尚未得到评估。我们进行了这项回顾性研究，以评估在二线或更晚的治疗中，抗 PD-1/L1 联合抗血管生成治疗在晚期肺腺癌患者中的疗效和安全性。

方法

回顾性分析 2015 年 3 月至 2019 年 5 月期间在中国人民解放军总医院接受二线或更晚的抗 PD-1/L1 联合抗血管生成治疗或抗 PD-1/L1 单药治疗的晚期肺腺癌患者。评估无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）和安全性。采用 Cox 比例风险回归模型对 PFS 和 OS 进行多因素分析。

结果

本研究共纳入 74 例患者。25 例患者接受抗 PD-1/L1 联合抗血管生成治疗，49 例患者接受抗 PD-1/L1 单药治疗。抗 PD-1/L1 联合抗血管生成组的疾病控制率（DCR）高于抗 PD-1/L1 单药治疗组（92.0% vs. 46.9%，P=0.0004）。抗 PD-1/L1 联合抗血管生成组的中位无进展生存期（PFS）为 5.1 个月，而抗 PD-1/L1 单药治疗组为 2.0 个月（HR 0.551[95%置信区间 0.337-0.902]，P=0.002），中位总生存期（OS）分别为 14.3 个月和 8.4 个月（HR 0.549[95%CI 0.305-0.990]，P=0.046）。多因素 Cox 比例风险回归模型显示，抗 PD-1/L1 联合抗血管生成组 PFS 延长（HR 0.541[95%CI 0.298-0.981]，P=0.033）。抗 PD-1/L1 联合抗血管生成组 3 级/4 级不良事件发生率为 12%（3/25），抗 PD-1/L1 单药治疗组为 6%（3/49）。