白蛋白紫杉醇加卡铂联合抗血管生成药物用于经治的晚期黑色素瘤的疗效和安全性分析  

Treatment efficacy and safety profile of Nab-paclitaxel and carboplatin combined with antiangiogenic drugs as salvage regimen in advanced melanoma patients

作　　者：毛丽丽[1] 白雪[1] 代杰[1] 崔传亮[1] 迟志宏[1] 唐碧霞[1] 孔燕[1] 连斌[1] 王轩[1] 魏晓婷 李彩莉 郭军[1] 斯璐[1] MAO Lili;BAI Xue;DAI Jie;CUI Chuanliang;CHI Zhihong;TANG Bixia;KONG Yan;LIAN Bin;WANG Xuan;WEI Xiaoting;LI Caili;GUO Jun;SI Lu(Key laboratory of Carcinogenesis and Translational Research,Ministry of Education/Beijing,Department of Melanoma,Peking University Cancer Hospital&Institute,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所黑色素瘤内科恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《中国肿瘤生物治疗杂志》2021年第12期1194-1200,共7页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.81972566;No.82073011;No.81972562);北京自然科学基金资助项目(No.7202024);北京市医院管理局“登峰”人才培养计划资助项目(No.DFL20181101);临床医学+X青年专项基金资助项目(No.PKU2019LCXQ017);北京医学奖励基金会资助项目(No.YXJL-2019-0079-0052);希思科-石药肿瘤研究基金资助项目(No.Y-SY201901-0270)。

摘　　要：目的:本研究旨在评估白蛋白紫杉醇+卡铂联合抗血管生成药物(nab-paclitaxel,carboplatin,antiangiogenic drug,NCA)方案用于既往治疗失败的晚期黑色素瘤患者的疗效和安全性。方法:收集2012年4月1日至2019年5月31日在北京大学肿瘤医院肾癌黑色素瘤科住院的黑色素瘤患者,回顾性分析NCA方案在既往治疗失败后的不可切除Ⅲc期和Ⅳ期黑色素瘤患者中的疗效和安全性。主要终点指标为无进展生存期(PFS),次要指标为客观缓解率(ORR)、总生存期(OS)、疾病控制率(DCR)和不良反应。根据使用的抗血管药物分为恩度治疗组(n=73)和贝伐珠单抗治疗组(n=103),采用倾向性评分匹配以均衡不同抗血管生成药物组间基线变量的差异。结果:共计176例患者被纳入本项分析中。所有患者中位年龄51岁(范围为18~78岁)。Ⅳ期患者占97%,50%的患者LDH水平高于正常值,28%的患者存在肝转移。既往治疗线数占比分别为1线57%、2线33%、3~4线10%。所有患者的中位PFS为3.8个月(95%CI:3.0~4.6),中位OS为10.5个月(95%CI:8.9~12.1)。2例患者获得完全缓解,9例患者获得部分缓解,全组的ORR为6%,DCR达70%。恩度治疗组和贝伐珠单抗治疗组的中位PFS分别为4.7个月(95%CI:3.5~5.9)和3.4个月(95%CI:3.0~4.6),两组中位OS分别为12.2个月(95%CI:11.1~13.2)和9.1个月(95%CI:7.8~10.4)。对所有患者的年龄、性别、既往治疗线数和LDH水平进行倾向性评分匹配,贝伐珠单抗和恩度治疗组间PFS和OS差异无统计学意义。常见的不良反应包括脱发、周围神经病变、中性粒细胞减少、疲劳和恶心。26名(15%)患者由于不良反应停止了治疗。结论:白蛋白紫杉醇+卡铂联合抗血管生成药物对既往治疗失败的晚期黑色素瘤患者具有一定的疗效,不良反应可耐受。Objective: To evaluate the treatment efficacy and safety profile of NCA regimen(nab-paclitaxel, carboplatin and antiangiogenic drug) in advanced melanoma patients who failed previous therapy. Methods: We retrospectively enrolled the melanoma patients who were treated in the Department of Melanoma of Peking University Cancer Hospital from April 1, 2012 to March 31, 2019 and investigated the efficacy and safety of NCA regimen in unresectable stage IIIC or IV melanoma patients who failed previous therapy. The primary endpoint was the progression-free survival(PFS), and the secondary indicators were objective response rate(ORR), overall survival(OS), disease control rate(DCR) and adverse reactions. The patients were divided into endostatint treatment group(Endo-arm, n=73) and bevacizumab treatment group(Beva-arm, n=103) according to the antiangiogenic drug used in the regimen. Propensity score matching was applied to balance the differences in baseline covariates between different antiangiogenic drug groups. Results: Overall, 176 patients were included in this study. The median age of included patients was 51 years old(18-78). Stage IV patients accounted for 97%. There were 50% patients with higher LDH level than normal, and 28% patients with liver metastasis.The proportions of lines of previous treatment were 57% for first line treatment, 33% for second line and 10% for third-fourth line. The median PFS was 3.8 months(95% CI: 3.0–4.6 m) and median OS was 10.5 months(95% CI: 8.9-12.1 m) in overall study population.There were 9 PR(partial remission) cases and 2 CR(complete remission) cases, yielding an overall ORR of 6% with a DCR of 70%.The median PFS of Endo-arm and Beva-arm was 4.7 months(95%CI:3.5~5.9 m) and 3.4 months(95%CI: 3.0~4.6 m) respectively, while the median OS was 12.2 months(95%CI: 11.1~13.2 m) and 9.1 months(95%CI: 7.8~10.4 m) respectively. After the age, gender, lines of previous treatment and LDH level of patients were adjusted by propensity score matching, there were no statistical differences in

关 键 词：黑色素瘤 白蛋白紫杉醇 卡铂 贝伐单抗 血管内皮抑制素 

分 类 号：R739.5[医药卫生—肿瘤] R730.54[医药卫生—临床医学]