Real-world efficacy and safety of axitinib in combination with anti-programmed cell death-1 antibody for advanced mucosal melanoma
Real-world efficacy and safety of axitinib in combination with anti-programmed cell death-1 antibody for advanced mucosal melanoma
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DOI：
10.1016/j.ejca.2021.07.018
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发表时间：
2021-08-20
影响因子：
8.4
通讯作者：
Sheng, Xinan
中科院分区：
文献类型：
--
作者：
Tang, Bixia;Mo, Jiazhi;Sheng, Xinan
目的：血管内皮生长因子受体(VEGFR)抑制剂和程序性细胞死亡-1(PD-1)阻断的联合应用为晚期粘膜黑色素瘤的早期试验提供了良好的治疗机会。这项回顾性研究的目的是评估联合方案在现实世界中治疗晚期粘膜黑色素瘤的有效性和安全性。方法：晚期粘膜黑色素瘤患者接受抗PD-1抗体和VEGFR抑制剂Axitinib治疗，直到确认病情进展或不良反应不可接受。此外，肝转移患者还可以接受肝动脉化疗栓塞术(TACE)。主要终点为总有效率(ORR)。次要终点包括疾病控制率(DCR)、治疗失败时间(TTF)、有效时间(DOR)、总生存期(OS)和治疗相关不良事件(TRAE)。结果：81例患者接受了阿西替尼联合免疫治疗，66例患者接受了抢救治疗。总的ORR为24.5%(95%CI，17.3~31.6)，DCR为72.7%(95%CI，65.3~80.1)。中位TTF、DOR和OS分别为5.2个月(95%可信区间，3.7~6.6)、9.2个月(95%可信区间，7.2~11.2)和11.1个月(95%可信区间，7.2~15.0)。一线治疗和抢救治疗的ORR分别为30.0%(95%CI，19.7~40.3)和17.5%(95%CI，7.8~27.1)。ORR在各原发部位间无统计学差异。合并或不合并肝动脉化疗栓塞者的ORR分别为26.1%(95%CI，6.7~45.5)和15.0%(95%CI，2.1~32.1)，P<0.467。LDH升高和ECOG状态差是负面预测因素。结论：这是迄今为止最大规模的抗PD-1联合VEGFR抑制剂治疗黏膜黑色素瘤的研究。免疫治疗加抗血管生成适用于晚期粘膜黑色素瘤，尤其是作为一线治疗。肝动脉化疗栓塞术可能与全身免疫治疗和抗血管生成有协同作用。2021爱思唯尔有限公司，版权所有。
Purpose: The combination of vascular endothelial growth factor receptor (VEGFR) inhibitor and programmed cell death-1 (PD-1) blockade provides promising therapeutic opportunities for advanced mucosal melanoma in early phase trials. The aim of this retrospective study was to evaluate the efficacy and safety of the combination regimen for advanced mucosal melanoma in the real world. Methods: Patients with advanced mucosal melanoma received an anti-PD-1 antibody plus the VEGFR inhibitor axitinib until confirmed disease progression or unacceptable toxicity. In addition, those with liver metastasis were allowed to take hepatic transcatheter arterial chemoembolisation (TACE). The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), time to treatment failure (TTF), duration of response (DOR), overall survival (OS) and treatment-related adverse events (TRAEs). Results: Eighty-one and sixty-six patients received axitinib plus immunotherapy as first-line and salvage therapy, respectively. Overall, ORR was 24.5% (95% CI, 17.3-31.6), DCR was 72.7% (95% CI, 65.3-80.1). Median TTF, DOR and OS were 5.2 months (95% CI, 3.7-6.6), 9.2 months (95% CI, 7.2-11.2 ) and 11.1 months (95% CI, 7.2-15.0). ORR was 30.0% (95% CI, 19.7-40.3) and 17.5% (95% CI, 7.8-27.1) as first-line and salvage therapy, respectively. No statistical difference among the primary sites was noted for ORR. The ORR of patients with liver metastasis with or without hepatic TACE was 26.1% (95% CI, 6.7-45.5) and 15.0% (95% CI, 2.1-32.1), respectively (P Z 0.467). Elevated LDH and poor ECOG status are negative predictive factors. Conclusion: This is the largest analysis of anti-PD-1 plus VEGFR inhibitor therapy for mucosal melanoma to date. Immunotherapy plus anti-angiogenesis is applicable for advanced mucosal melanoma, especially as front-line. Hepatic TACE might act synergistically with systemic immunotherapy and anti-angiogenesis. 2021 Elsevier Ltd. All rights reserved.