Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy
Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy
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DOI：
10.1016/j.ejca.2018.11.015
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发表时间：
2019-01-01
影响因子：
8.4
通讯作者：
Mesia, Ricard
中科院分区：
文献类型：
--
作者：
Zandberg, Dan P.;Algazi, Alain P.;Mesia, Ricard
背景资料：接受铂类化疗后进展的复发性/转移性头颈部鳞状细胞癌（R/M HNSCC）患者预后较差，治疗选择有限。程序性细胞死亡-1（PD-1）及其配体1（PD-L1）在HNSCC中经常上调。国际、多机构、单组、II期HAWK研究（NCT 02207530）在患有铂难治性R/M HNSCC的PD-L1高患者中评估了durvalumab单一疗法（一种抗PD-L1单克隆抗体）。经证实肿瘤细胞PD-L1高表达的免疫治疗初治患者（定义为使用VENTANA PD-L1 [SP263] Assay，肿瘤细胞表达PD-L1 [TC >= 25%]的患者）接受durvalumab 10 mg/kg静脉给药，每2周一次，持续12个月。主要终点为客观缓解率，次要终点为无进展生存期（PFS）和总生存期（OS）（95%置信区间[CI]，9.9-24.4）;人乳头瘤病毒（HPV）阳性患者为29.4%（95% CI，15.1-47.5），HPV阴性患者为10.9%（95% CI，4.5-21.3）。接受治疗的患者（n = 112）的中位PFS和OS分别为2.1个月（95% CI，1.9-3.7）和7.1个月（95% CI，4.9-9.9）; 12个月时的PFS和OS分别为14.6%（95% CI，8.5-22.1）和33.6%（95% CI，24.8-42.7）。治疗相关不良事件发生率为57.1%（任何级别）和8.0%（≥ 3级）;无一例导致死亡。在数据截止日期，24.1%的患者仍在治疗或follow-up.Conclusion：Durvalumab在PD-L1高的R/M HNSCC患者中表现出抗肿瘤活性和可接受的安全性，支持其在第一和第二线环境中的III期试验中正在进行的评估。在一项特别分析中，HPV阳性患者的缓解率和生存率在数值上高于HPV阴性患者。(C)2018作者由爱思唯尔有限公司出版。这是一篇在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Background: Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC.Patients and methods: Immunotherapy-naive patients with confirmed PD-L1-high tumour cell expression (defined as patients with >= 25% of tumour cells expressing PD-L1 [TC >= 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS).Results: Among evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9-24.4); 29.4% (95% CI, 15.1-47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5-21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9-3.7) and 7.1 months (95% CI, 4.9-9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5-22.1) and 33.6% (95% CI, 24.8-42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade >= 3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up.Conclusion: Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients. (C) 2018 The Authors. 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/).