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Ⅲ c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:3.5~5.9m) and 3.4 months (95%CI: 3.0~4.6m) respectively, while the median OS was 12.2 months (95%CI: 11.1~13.2m) and 9.1 months (95%CI: 7.8~10.4m) 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 PFS and OS between Beva-arm and Endo-arm. Common adverse events included alopecia, peripheral neuropathy, neutropenia, fatigue and nausea. 26 patients (15%) discontinued treatment adverse events. Conclusion: The NCA regimen shows modest antitumor effects in melanoma patients who failed previous treatment, due to and the adverse reactions were acceptable.

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）。