Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742)
Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742)
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DOI：
10.1200/jco.2017.77.0388
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发表时间：
2018-05-10
影响因子：
45.3
通讯作者：
Chan, Anthony T. C.
中科院分区：
文献类型：
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作者：
Ma, Brigette B. Y.;Lim, Wan-Teck;Chan, Anthony T. C.
目的评价纳武利尤单抗（nivolumab）对鼻咽癌（nasopharyngeal carcinoma，NPC）的抗肿瘤活性。肿瘤和血浆为基础的生物标志物进行了调查，在一个探索性analysis.Patients和MethodsPatients多次预处理复发或转移性NPC与nivolumab治疗，直到疾病进展。主要终点为客观缓解率（ORR），次要终点包括生存率和毒性。程序性死亡配体1（PD-L1）和人类白细胞抗原A和B在存档的肿瘤和EB病毒DNA的血浆清除率的表达与ORR和survival.ResultsA共44例患者进行了评价，总体ORR为20.5%（完全反应，n = 1;部分反应，n = 8）。9名患者接受nivolumab治疗> 12个月（20%）。1年总生存率为59%（95% CI，44.3%-78.5%），1年无进展生存率（PFS）为19.3%（95% CI，10.1%-37.2%）。ORR与生物标志物之间无统计学相关性;然而，描述性分析显示，PD-L1阳性肿瘤（表达> 1%）患者的缓解比例高于PD-L1阴性肿瘤患者。一种或两种人类白细胞抗原1类蛋白表达缺失与PFS比两种蛋白表达时更好相关（1年PFS，30.9% vs 5.6%;对数秩P = .01）。存活率与PD-L1表达或血浆EB病毒DNA清除率之间无相关性。有没有意想不到的毒性nivolumab.ConclusionNivolumab在NPC和1年的总生存率相比，有利的历史数据在类似的人群中具有很好的活性。需要在随机环境中进行额外评价。生物标志物结果是假设生成的，需要在更大的队列中进行验证。
PurposeThis multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis.Patients and MethodsPatients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival.ResultsA total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for > 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (> 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab.ConclusionNivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.