Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An interim analysis of a postmarketing surveillance
Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An interim analysis of a postmarketing surveillance
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DOI：
10.1111/1346-8138.14227
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发表时间：
2018-04-01
影响因子：
3.1
通讯作者：
Yamazaki, Naoya
中科院分区：
文献类型：
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作者：
Kiyohara, Yoshio;Uhara, Hisashi;Yamazaki, Naoya
一项上市后监测研究正在进行中，以评估纳武单抗对日本恶性黑色素瘤患者的治疗，并积累所有不良事件 (AE) 和疗效的数据。在这项中期分析中，我们评估了从日本纳武单抗批准日期（2014 年 7 月 4 日）到 2016 年 7 月 3 日期间从大约 100 个日本医疗机构获得的数据。在治疗的前 12 个月期间对患者进行了监测。纳武单抗通过静脉注射给药。输注（每 3 周 2 毫克/千克）。总共分别评估了 680 名和 610 名患者的安全性和有效性。药品不良反应（ADR）和3级及以上ADR发生率分别为53.53%和12.35%。主要不良反应包括甲状腺功能减退症（11.32%）和酶活性异常，如天冬氨酸转氨酶（7.79%）、丙氨酸转氨酶（6.76%）、碱性磷酸酶（6.18%）和谷氨酰转移酶（5.44%）升高。发生率1%或以上的3级或以上ADR为肝功能障碍（2.50%）、结肠炎/腹泻（2.06%）和输液反应（1.32%）。没有观察到脑炎或静脉血栓栓塞以及其他特别关注的 AE 病例。总体人群的估计中位总生存期为 379 天（95% 置信区间 [CI]，290-未达到 [NR]），皮肤黑色素瘤为 NR（95% CI，305-NR），粘膜黑色素瘤为 340 天（95% CI，275-NR）。根据上次评估的抗肿瘤反应，改善率为 22.2%（131/590 名患者）。没有提出新的安全问题，并且很少出现特别令人关注的严重不良反应。纳武单抗对粘膜黑色素瘤和皮肤黑色素瘤患者显示出相同的疗效。
A postmarketing surveillance study is ongoing to evaluate nivolumab treatment for Japanese patients with malignant melanoma and accumulate data on all adverse events (AE) and efficacy. In this interim analysis, we evaluated data from approximately 100 Japanese medical institutions obtained from the nivolumab approval date in Japan (4 July 2014) through 3 July 2016. Patients were monitored during the first 12 months of treatment. Nivolumab was administrated by i.v. infusion (2 mg/kg every 3 weeks). A total of 680 and 610 patients were evaluated for safety and efficacy, respectively. The incidences of adverse drug reactions (ADR) and grade 3 or higher ADR were 53.53% and 12.35%, respectively. Predominant ADR included hypothyroidism (11.32%) and abnormal enzyme activity, such as increase of aspartate aminotransferase (7.79%), alanine aminotransferase (6.76%), alkaline phosphatase (6.18%) and -glutamyltransferase (5.44%). Grade 3 or higher ADR of special interest with an incidence of 1% or higher were hepatic function disorder (2.50%), colitis/diarrhea (2.06%) and infusion reaction (1.32%). No cases of encephalitis or venous thromboembolism, other AE of special interest, were observed. The estimated median overall survival was 379 days (95% confidence interval [CI], 290-not reached [NR]) in the overall population, NR (95% CI, 305-NR) for cutaneous melanoma and 340 days (95% CI, 275-NR) for mucosal melanoma. The improvement rate based on the antitumor response at the last evaluation was 22.2% (131/590 patients). No new safety concerns were raised, and serious ADR of special interest were infrequent. Nivolumab showed equivalent efficacy in patients with mucosal melanoma and those with cutaneous melanoma.