An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck
An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck
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DOI：
10.1007/s00280-014-2459-z
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发表时间：
2014-06-01
影响因子：
3
通讯作者：
Gauler, Thomas C.
中科院分区：
文献类型：
--
作者：
Saloura, Vassiliki;Cohen, Ezra E. W.;Gauler, Thomas C.
铂类难治性复发性或转移性头颈部鳞状细胞癌(R/M SCCHN)患者的治疗选择有限。本研究的目的是评价扎鲁单抗治疗铂类难治性R/M SCCHN的疗效和安全性。选择功能状态为0~2、年龄<18岁、器官功能正常的难治性R/M SCCHN患者。患者每周接受扎鲁单抗滴定至2级皮疹。首要目标是总体生存(OS)，次要目标是疗效和安全性。对人口统计学、疾病相关和分子因素进行了OS和无进展生存(PFS)的亚组分析。纳入90名患者。23%的患者表现状态(PS)为2，74%的患者有远处转移。中位OS为5.3个月(95%CI[4.1，7.1])，中位PFS为2.1个月(95%CI[2.0，2.6])。经ECOG PS亚组分析，PS=0~1的中位OS为6.3个月，PS=2的中位OS为2.5个月。客观有效率为5.7%，疾病控制率为39.8%。19%的患者观察到与扎鲁单抗有关的3-4级不良反应，包括皮疹(5%)、低镁血症(4%)和肺炎(1%)。全因3-4级不良反应的发生率为62%，包括感染(14%)、胃肠道疾病(12%)和低钾血症(6%)。两例死亡被认为与Zalutumab[ClinicalTrials.gov标识符：NCT00542308]有关。Zalutumab对铂类难治性R/M SCCHN患者显示出合理的疗效，基于皮疹评估的剂量滴定是可行的。
Treatment options for patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) are limited. The purpose of this study was to assess the efficacy and safety of zalutumumab in platinum-refractory R/M SCCHN.Patients with platinum-refractory R/M SCCHN were enrolled if they had performance status of 0-2, age a parts per thousand yen18 years and adequate organ function. Patients received weekly infusions of zalutumumab individually titrated to a grade 2 skin rash. Primary objective was overall survival (OS), and secondary objectives were efficacy and safety. A subgroup analysis of OS and progression-free survival (PFS) was conducted for various demographic, disease-related and molecular factors.Ninety patients were enrolled. Twenty-three percent of patients had performance status (PS) 2 and 74 % had distant metastases. Median OS was 5.3 months (95 % CI [4.1, 7.1]), and median PFS was 2.1 months (95 % CI [2.0, 2.6]). Subgroup analysis by ECOG PS revealed median OS of 6.3 months for PS = 0-1 and 2.5 months for PS = 2. Objective response rate was 5.7 %, and disease control rate was 39.8 %. Grade 3-4 adverse events related to zalutumumab were observed in 19 % of patients and included skin rash (5 %), hypomagnesemia (4 %) and pneumonitis (1 %). The frequency of all-cause grade 3-4 AEs was 62 % and included infections (14 %), gastrointestinal disorders (12 %) and hypokalemia (6 %). Two deaths were deemed related to zalutumumab [ClinicalTrials.gov Identifier: NCT00542308].Zalutumumab showed reasonable efficacy in platinum-refractory R/M SCCHN patients, and dose titration based on skin rash evaluation was feasible.