PD-1抑制剂联合安罗替尼治疗化疗后进展的晚期食管鳞状细胞癌的回顾性研究

Efficacy and safety of PD-1 inhibitor combined with anlotinib for advanced esophageal squamous cell carcinoma that progressed after chemotherapy:a retrospective study

目的:观察程序性死亡因子受体-1(programmed death receptor 1,PD-1)抑制剂联合安罗替尼在晚期食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)患者后线治疗中的疗效及安全性。方法:经过化疗后进展的晚期ESCC患者接受PD-1抑制剂联合安罗替尼治疗,直至疾病进展或不能耐受。主要研究终点为无进展生存(progression-free survival,PFS),次要研究终点为客观缓解率(objective response rate,ORR)及总生存(overall survive,OS)。随访截止到2021年11月30日。结果:2019年3月至2021年7月郑州大学附属肿瘤医院共63例ESCC患者接受了PD-1抑制剂联合安罗替尼治疗,中位无进展生存(median progression-free survival,mPFS)为7.1个月(95%CI:4.3~9.9),ORR为14.3%,疾病控制率(disease control rate,DCR)为69.8%,中位总生存(median overall survival,mOS)尚未达到。不良反应主要为乏力31例(49.2%)、甲状腺功能减退29例(46.0%)、高血压24例(38.1%)、恶心和呕吐22例(34.9%)、手足综合征21例(33.3%)、皮疹20例(31.7%)。3级不良反应有出血及穿孔3例(4.8%)、间质性肺炎2例(3.2%)、甲状腺功能减退2例(3.2%)、免疫心肌炎1例(1.6%)、皮疹1例(1.6%)、腹泻1例(1.6%)等。未观察到4级不良反应及治疗相关死亡事件的发生。结论:PD-1抑制剂联合安罗替尼在晚期化疗后进展的ESCC治疗中显示出显著的疗效及良好的安全性,可作为ESCC患者后线治疗的选择。

Objective:To analyze the efficacy and safety of programmed death receptor 1(PD-1)inhibitor combined with anlotinib as post-line therapy for patients with advanced esophageal squamous cell carcinoma(ESCC).Methods:We examined patients with advanced ESCC who were treated with PD-1 inhibitor combined with anlotinib until disease progression or intolerance.The primary endpoint was progression-free survival(PFS).The secondary endpoints were objective response rate(ORR)and overall survival(OS).The last follow-up was conducted on November 30,2021.Results:From March 2019 to July 2021,63 patients met the inclusion criteria and received PD-1 inhibitor combined with anlotinib at Affiliated Cancer Hospital of Zhengzhou University.The median progression-free survival(mPFS)was 7.1 months(95%CI:4.3–9.9).The ORR and disease control rate(DCR)were 14.3%and 69.8%,respectively.The median overall survival(mOS)had not yet been reached.Adverse events included fatigue(49.2%),hypothyroidism(46.0%),hypertension(38.1%),nausea and vomiting(34.9%),hand-foot syndrome(33.3%),and rash(31.7%).Grade 3 adverse reactions included bleeding and perforation(4.8%),interstitial pneumonia(3.2%),hypothyroidism(3.2%),immunocarditis(1.6%),rash(1.6%),and diarrhea(1.6%).No grade 4 adverse reactions or treatment-related deaths occurred.Conclusions:PD-1 inhibitor combined with anlotinib shows significant efficacy and good safety for treating ESCC that progresses after advanced chemotherapy.The therapy could also be a post-line therapy option for patients with ESCC.