化疗联合PD-1抑制剂在晚期黑色素瘤患者中的疗效和安全性分析  

Efficacy and safety of chemotherapy plus PD-1 inhibitor in patients with advanced melanoma

作　　者：田慧 连斌 斯璐[1] 迟志宏[1] 盛锡楠[1] 崔传亮[1] 郭军[1] TIAN Hui;LIAN Bin;SI Lu;CHI Zhihong;SHENG Xi'nan;CUI Chuanliang;GUO Jun(Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.)

机构地区：[1]北京大学临床肿瘤学院,北京肿瘤医院暨北京市肿瘤防治研究所,恶性肿瘤发病机制及转化研究教育部重点实验室肾癌与黑色素瘤科,北京100142

出　　处：《临床肿瘤学杂志》2021年第9期816-821,共6页Chinese Clinical Oncology

基　　金：国家自然科学基金面上项目(81972562);北京市属医院科研培育项目(PX2017042,PX2021046);北京市医院管理中心“青苗”计划专项经费资助(QML20181101)。

摘　　要：目的探索化疗联合程序性死亡受体1(PD-1)抑制剂在中国人群晚期黑色素瘤患者中的有效性及安全性。方法收集2019年2月至2020年2月在北京大学肿瘤医院确诊为不可切除的晚期黑色素瘤患者50例,接受替莫唑胺(200 mg/m2)或白蛋白结合型紫杉醇(260 mg/m2)联合PD-1抑制剂(特瑞普利单抗240 mg,d1,每2周1次或帕博利珠单抗100 mg,d1,每3周1次)治疗。观察患者的近期疗效、总生存期(OS)、无进展生存期(PFS)及不良反应。结果50例患者中,46例可评价疗效。获CR 1例,PR 12例,SD 22例,客观有效率(ORR)为28.3%(13/46),疾病控制率(DCR)为76.1%(35/46)。替莫唑胺联合PD-1抑制剂组和白蛋白结合型紫杉醇联合PD-1抑制剂组的ORR分别为23.8%(5/21)、32.0%(8/25),但差异无统计学意义(P>0.05)。至随访截止日期,全组患者的中位OS未达,中位PFS为5.4个月(95%CI:2.6~8.2个月)。替莫唑胺联合PD-1抑制剂组的中位PFS为6.5个月(95%CI:1.1~11.9个月),长于白蛋白结合型紫杉醇联合PD-1抑制剂组的4.0个月(95%CI:1.0~7.0个月),但两者差异无统计学意义(P>0.05)。生存单因素分析结果显示,联合不同化疗药物、不同病理类型、既往是否接受过免疫治疗均未影响患者的PFS(P>0.05)。不良反应多为1~2级,3级以上不良反应发生率为40.0%(20/50),多为血细胞减少。结论化疗联合PD-1抑制剂改善了中国晚期黑色素瘤患者的ORR、PFS,且耐受性良好,可进一步开展大样本随机对照研究证实。Objective To evaluate the efficacy and safety of chemotherapy plus programmed death receptor 1(PD-1)inhibitor in Chinese patients with advanced melanoma.Methods A total of patients with unresectable advanced melanoma diagnosed in Peking University Cancer Hospital from February 2019 to February 2020 were collected and received temozolomide(200 mg/m2)or albumin bound paclitaxel(260 mg/m2)combined with PD-1 inhibitor(toripalimab 240 mg,d1,once every 2 weeks or pembrolizumab 100 mg,d1,once every 3 weeks).The short-term efficacy,overall survival(OS),progression free survival(PFS)and adverse reactions were observed.Results Among the 50 patients,46 were evaluable for short-term efficacy.There was 1 patient with CR,12 patients with PR and 22 patients with SD.The objective response rate(ORR)was 28.3%(13/46),and the disease control rate(DCR)was 76.1%(35/46).The ORR of temozolomide combined with PD-1 inhibitor group and albumin bound paclitaxel combined with PD-1 inhibitor group were 23.8%(5/21)and 32.0%(8/25),respectively,but the difference was not statistically significant(P>0.05).By the end of follow-up,the median OS of 50 patients was not reached,and the median PFS was 5.4 months(95%CI:2.6-8.2 months).The median PFS of temozolomide combined with PD-1 inhibitor group was 6.5 months(95%CI:1.1-11.9 months),which was longer than 4.0 months(95%CI:1.0-7.0 months)of albumin bound paclitaxel combined with PD-1 inhibitor group,but there was no significant difference between the two groups(P>0.05).Univariate analysis of survival showed that the combination of different chemotherapeutic drugs,different pathological types and previous immunotherapy did not affect the PFS of patients(P>0.05).Most adverse events were grade 1 or 2,and the incidence of adverse reactions above grade 3 was 40.0%(20/50),mostly hematopenia.Conclusion Chemotherapy combined with PD-1 inhibitor in Chinese patients with advanced melanoma has good outcome with mild adverse events,which can be further confirmed by large sample randomized controlled study.

关 键 词：晚期黑色素瘤 PD-1抑制剂 化学治疗 联合治疗 

分 类 号：R739.5[医药卫生—肿瘤]