Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT)
Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT)
复制标题
DOI：
10.1158/1078-0432.ccr-19-0103
复制
发表时间：
2019-09-01
影响因子：
11.5
通讯作者：
Ohe, Yuichiro
中科院分区：
文献类型：
--
作者：
Okada, Morihito;Kijima, Takashi;Ohe, Yuichiro
目的：恶性胸膜间皮瘤是一种少见的恶性肿瘤，侵袭性强，预后差。对标准一线化疗无反应的MPM患者的治疗选择有限。我们评估了nivolumab，免疫检查点抑制剂，用于治疗晚期或转移性MPM.Patients和方法的疗效和安全性：日本患者不可切除，晚期或转移性MPM耐药或不耐受= 1可测量的病变（S）被招募。患者每2周一次静脉内接受纳武利尤单抗240 mg，直至疾病进展或出现不可接受的毒性。主要终点是根据改良的实体瘤疗效评价标准进行的中心评估的客观缓解率。对不良事件（AE）和治疗相关AE（TRAE）进行了评估。结果：2016年7月至2016年10月期间入组了34例患者。中位随访时间为16.8（范围：1.8-20.2）个月。10例（29%，95%置信区间，16.8-46.2）患者显示中心评估的客观缓解。上皮样、肉瘤样和双相组织学亚型的客观缓解率分别为26%（7/27）、67%（2/3）和25%（1/4）。中位缓解持续时间为11.1个月，疾病控制率为68%。中位总生存期和无进展生存期分别为17.3和6.1个月。程序性死亡配体1表达>= 1%的患者客观缓解率为40%，
Purpose: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor prognosis. Patients with MPM who do not respond to standard first-line chemotherapy have limited treatment options. We evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for the treatment of advanced or metastatic MPM.Patients and Methods: Japanese patients with unresectable, advanced, or metastatic MPM resistant or intolerant to = 1 measurable lesion (s) were enrolled. Patients received nivolumab 240 mg intravenously every 2 weeks until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate by central assessment according to the Modified Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) and treatment-related AEs (TRAEs) were evaluated.Results: Thirty-four patients were enrolled between July 2016 and October 2016. Median follow-up was 16.8 (range: 1.8-20.2) months. Ten (29%, 95% confidence interval, 16.8-46.2) patients showed a centrally assessed objective response. The objective response rates were 26% (7/27), 67% (2/3), and 25% (1/4) patients for epithelioid, sarcomatoid, and biphasic histologic subtypes, respectively. Median duration of response was 11.1 months with a 68% disease control rate. Median overall survival and progression-free survival were 17.3 and 6.1 months, respectively. The objective response rate was 40% with programmed death-ligand 1 expression >= 1% and 8% with