PD-1单抗治疗晚期HER-2阴性胃癌的临床观察

Clinical observation of PD-1 inhibitors on advanced HER-2 negative gastric cancer

目的探讨程序性死亡受体-1(PD-1)单抗单药及联合化疗和/或抗血管生成药物治疗晚期人类表皮生长因子受体2(HER-2)阴性胃癌的疗效及安全性。方法回顾性分析2019年1月至2020年12月80例经组织病理学确诊的晚期HER-2阴性胃腺癌患者的临床资料。80例患者中9例仅接受PD-1单抗治疗,20例接受PD-1单抗联合化疗,23例接受PD-1单抗联合抗血管生成治疗,28例接受PD-1单抗联合化疗及抗血管生成治疗。分析接受不同治疗方案和治疗线数患者的近期疗效、远期疗效和不良反应。结果80例患者中无CR病例,获PR 15例、SD 34例、PD 31例,有效率(RR)为18.8%,疾病控制率(DCR)为61.2%。中位随访7个月,中位无进展生存期(PFS)为3.0(95%CI:2.8~3.2)个月,其中二线治疗(n=40)的DCR为77.5%,中位PFS为4.0(95%CI:2.9~5.1)个月,优于三线治疗(n=26)的46.2%和3.0(95%CI:2.3~3.7)个月,以及四线及多线治疗(n=14)的42.8%和2.2(95%CI:1.3~3.1)个月(P=0.005)。PD-1单抗联合化疗及抗血管生成治疗组(n=28)的中位PFS为4.0(95%CI:1.7~6.3)个月,仅接受单药PD-1单抗治疗组的中位PFS为3.0(95%CI:0.9~5.1)个月,联合化疗组为3.0(95%CI:2.6~3.4)个月,联合抗血管生成治疗组为3.0(95%CI:2.1~3.9)个月,差异有统计学意义(P=0.027)。全组主要不良反应包括贫血、乏力、转氨酶升高、纳差、中性粒细胞减少,以1~2级为主,3例患者因3~4级不良反应终止治疗。结论PD-1单抗联合治疗用于晚期HER-2阴性胃癌疗效确切,安全性良好,且越早线使用患者获益越明显。PD-1单抗联合化疗及抗血管生成治疗模式值得临床进一步探索。

Objective To investigate the efficacy and safety of programmed death 1(PD-1)inhibitor monotherapy and combined chemotherapy and/or anti-angiogenic drugs in the treatment of human epidermal growth factor receptor 2(HER-2)negative advanced gastric cancer.Methods The clinical data of 80 patients with HER-2 negative advanced gastric cancer diagnosed by histopathology from January 2019 to December 2020 were reviewed.Among them,9 patients received PD-1 inhibitor monotherapy,20 patients received PD-1 inhibitor combined with chemotherapy,23 patients received PD-1 inhibitor combined with anti-angiogenesis therapy,28 patients received PD-1 inhibitor combined with chemotherapy and anti-angiogenesis therapy.The short-term efficacy,long-term efficacy and safety of patients receiving different treatment schemes and the number of treatment lines were analyzed.Results During the median follow-up of 7 months,no complete response case was observed.Number of patients who reached PR,SD and PD were 15,34 and 31,respectively.The response rate(RR)of 80 patients was 18.8%,the disease control rate(DCR)was 61.2%,and the median progression-free survival(PFS)was 3.0(95%CI:2.8-3.2)months.The DCR of second-line therapy(n=40)was 77.5%and the median PFS was 4.0(95%CI:2.9-5.1)months,better than 46.2%and 3.0(95%CI:2.3-3.7)months of third-line therapy(n=26),and 42.8%and 2.2(95%CI:1.3-3.1)months of fourth-line and multi-line therapy(n=14).The difference was significant among them(P=0.005).The median PFS was 4.0(95%CI:1.7-6.3)months of PD-1 inhibitor combined with chemotherapy and anti-angiogenesis group(n=28),better than 3.0(95%CI:0.9-5.1)months of PD-1 inhibitor monotherapy group,3.0(95%CI:2.6-3.4)months of PD-1 inhibitor combined with chemotherapy group,and 3.0(95%CI:2.1-3.9)months of PD-1 inhibitor combined with anti-angiogenesis group(P=0.027).The main adverse reactions included anemia,fatigue,elevated transaminase,anorexia and neutropenia,mostly in grade 1-2.Treatment was terminated in 3 patients due to grade 3/4 adverse reactions.Conclusion PD-1 inhibitor combination therapy is effective and safe in the treatment of HER-2 negative advanced gastric cancer,and the earlier the therapy is used,the more benefit the patients will get.The mode of PD-1 inhibitor combined with chemotherapy and anti-angiogenesis therapy is worthy of further clinical exploration.