尼伏鲁单抗治疗复发性和转移性鼻咽癌的抗肿瘤活性：梅奥诊所第二阶段联盟（NCI-9742）的国际多中心研究。
Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742).
机构信息
Brigette B.Y. Ma, Edwin P. Hui, Kwok-Wai Lo, Ka-Fai To, K.C. Allen Chan, Y.M. Dennis Lo, Ann D. King, and Anthony T.C. Chan, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People's Republic of China; Wan-Teck Lim, National Cancer Centre; Boon-Cher Goh, National University Cancer Institute of Singapore; Alex Y.C. Chang, Johns Hopkins University School of Medicine; Akhil Chopra, OncoCare Cancer Centre, Singapore; Adam Pettinger, Nathan R. Foster, Charles Erlichman, Jun Yin, and Brian A. Costello, Mayo Clinic, Rochester, MN; Jonathan W. Riess, University of California Davis Comprehensive Cancer Center, Sacramento; Barbara J. Gitlitz, University of Southern California Keck School of Medicine, Los Angeles; Dean W. Lim, City of Hope Comprehensive Cancer Center, Duarte, CA; Mark Agulnik, Northwestern University, Evanston, IL; Julie A. Kish and Christine H. Chung, Moffitt Cancer Center, University of South Florida, Tampa, FL; Douglas R. Adkins, Washington University School of Medicine, St Louis, MO; Kevin J. Cullen, University of Maryland, Baltimore, MD.
出版信息
J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27.
Purpose This 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 Methods Patients 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. Results A 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. Conclusion Nivolumab 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.
目的 这项多中心研究评估了纳武利尤单抗在鼻咽癌（NPC）中的抗肿瘤活性。对肿瘤和血浆生物标志物进行了探索性分析。
方法 经多线治疗后复发或转移性 NPC 患者接受纳武利尤单抗治疗，直至疾病进展。主要终点为客观缓解率（ORR），次要终点包括生存和毒性。肿瘤组织中程序性死亡配体 1（PD-L1）和人类白细胞抗原 A、B 的表达以及血浆中 EBV-DNA 的清除率与 ORR 和生存相关。
结果 共 44 例患者接受了评估，总 ORR 为 20.5%（完全缓解 1 例，部分缓解 8 例）。9 例患者接受纳武利尤单抗治疗超过 12 个月（20%）。1 年总生存率为 59%（95%CI，44.3%至 78.5%），1 年无进展生存率（PFS）为 19.3%（95%CI，10.1%至 37.2%）。ORR 与生物标志物之间无统计学相关性，但描述性分析显示，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。与同时表达两种人类白细胞抗原 1 类蛋白相比，一种或两种蛋白表达缺失与更好的 PFS 相关（1 年 PFS：30.9%比 5.6%；log-rank P =.01）。PD-L1 表达或血浆 EBV-DNA 清除与生存均无相关性。纳武利尤单抗无意外毒性。
结论 纳武利尤单抗在 NPC 中具有良好的疗效，1 年总生存率与类似人群的历史数据相比具有优势。需要在随机对照环境中进一步评估。生物标志物结果为假说提供了依据，需要在更大的队列中进行验证。
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