Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study
Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study
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DOI：
10.1016/j.ejca.2018.09.025
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发表时间：
2018-12-01
影响因子：
8.4
通讯作者：
Yamazaki, Naoya
中科院分区：
文献类型：
--
作者：
Namikawa, Kenjiro;Kiyohara, Yoshio;Yamazaki, Naoya
目的：评价nivolumab联合ipilimumab治疗初治的日本晚期黑色素瘤患者的疗效和安全性。方法：在这项多中心、单臂研究中，初治的日本晚期黑色素瘤患者接受nivolumab(1 mg/kg)加ipilimumab(3 mg/kg)治疗，每3周1次，共4剂，之后每2周服用nivolumab(3 mg/kg)。主要终点为集中评估的客观反应率(ORR)。次要终点包括总生存期(OS)、无进展生存期(PFS)、疾病控制率和安全性。结果：30例患者中12例为粘膜型，8例为非肢端皮肤型，7例为肢端型，2例为葡萄膜型，1例为不明原因的原发黑色素瘤。经中央和地方评估，ORR为43.3%(95%可信区间：25.5，62.6)。中心和地方评估的疾病控制率(95%CI)分别为73.3%(54.1，87.7)和86.7%(69.3，96.2)。中位随访期为14.1个月(范围5.2-27.7个月)，未达到中位OS和集中评估的PFS。6、12、18、24个月OS(95%CI)分别为93.3%(75.9、98.3)、83.3%(64.5、92.7)、72.9%(50.0、86.5)、65.6%(40.4、82.2)。所有患者均发生治疗相关不良事件(AEs)。23例(76.7%)和20例(66.7%)患者发生III-IV级和严重不良反应，主要发生在联合期。没有发生与治疗相关的死亡。结论：这项研究证实了nivolumab联合ipilimumab治疗包括罕见亚型在内的日本晚期黑色素瘤的疗效和安全性。IIIeIV级AEs的发病率很高，但通过适当的医疗护理和治疗是可以控制的。试验注册号：JAPICCTI-152869。(C)2018年提交人(S)。由爱思唯尔有限公司出版。这是CC BY-NC-ND许可证(http://creativecommons.org/licenses/by-nc-nd/4.0/).下的一篇开放获取文章
Aim: The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naive Japanese patients with advanced melanoma.Methods: In this multicentre, single-arm study, treatment-naive Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety.Results: The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2-27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III-IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred.Conclusions: This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naive Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade IIIeIV AEs were high but manageable with appropriate medical attention and treatment. Trial registration: JapicCTI-152869. (C) 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).