Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis
Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis
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DOI：
10.1200/jco.2016.67.9258
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发表时间：
2017-01-10
影响因子：
45.3
通讯作者：
Wolchok, Jedd D.
中科院分区：
文献类型：
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作者：
D'Angelo, Sandra P.;Larkin, James;Wolchok, Jedd D.
目的粘液性黑色素瘤是一种侵袭性恶性肿瘤，常规治疗效果差。nivolumab的疗效和安全性（一种程序性死亡-1检查点抑制剂），单独使用或与易普利姆玛联合使用（一种细胞毒性T淋巴细胞抗原-4检查点抑制剂），尚未报道在这种罕见的黑色素瘤亚型中。86例（10%）患有粘膜黑素瘤，665例（75%）患有皮肤黑素瘤。还汇总了接受nivolumab联合ipilimumab治疗的患者的数据粘膜黑色素瘤35例;结果在接受nivolumab单药治疗的患者中，中位无进展生存期为3.0个月，（95% CI，2.2 - 5.4个月）和6.2个月（95% CI，5.1 - 7.5个月），客观缓解率为23.3%（95% CI，14.8%至33.6%）和40.9%（95% CI，37.1%至44.7%）。纳武单抗联合伊匹单抗治疗患者的中位无进展生存期为5.9个月（95% CI，2.8个月至未达到）和11.7个月（95% CI，8.9 - 16.7个月），客观缓解率为37.1%（95% CI，21.5%至55.1%）和60.4%（95% CI，54.9%至65.8%）。对于粘膜和皮肤黑色素瘤，分别为3级或4级治疗相关的不良事件的发生率为8.1%和12.5%的nivolumab单药治疗和40.0%和54.9%for combination therapy.ConclusionTo我们的知识，这是最大的分析数据抗程序性死亡-1治疗粘膜黑色素瘤的日期。纳武单抗联合伊匹单抗似乎比单独使用任何一种药物都具有更大的疗效，尽管在粘膜黑色素瘤中活性较低，但亚型之间的安全性特征相似。(C)2016年美国临床肿瘤学会
PurposeMucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype.Patients and MethodsData were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma).ResultsAmong patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy.ConclusionTo our knowledge, this is the largest analysis of data for anti-programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes. (C) 2016 by American Society of Clinical Oncology