在一项 EORTC 窗口术前研究中评估阿法替尼在头颈部鳞状细胞癌（SCCHN）患者中的活性和安全性。

Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

机构信息

Department of Medical Oncolog, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Italy; Department of Head and Neck Surger, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Italy; Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain, Brussels, Belgium.

Department of Head and Neck Medical Oncolog, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milan, Milan, Italy.

出版信息

Ann Oncol. 2018 Apr 1;29(4):985-991. doi: 10.1093/annonc/mdy013.

DOI:10.1093/annonc/mdy013

PMID:29346507

Abstract

BACKGROUND

To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN).

PATIENTS AND METHODS

This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR).

RESULTS

Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type.

CONCLUSION

Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov: NCT01538381.

摘要

背景

研究阿法替尼在头颈部鳞状细胞癌（SCCHN）术前治疗中的活性和安全性。

患者和方法

这是一项开放标签、随机、多中心、Ⅱ期机会窗试验。选择接受根治性手术的初治 SCCHN 患者，按 5:1 的比例随机（分配）接受阿法替尼治疗 14 天（-15 天至-1 天），直至手术前（0 天）或不治疗。在诊断时和手术前进行肿瘤活检、2-[氟-18]-氟-2-脱氧-d-葡萄糖正电子发射断层扫描（FDG-PET）和磁共振成像（MRI）。主要终点是代谢 FDG-PET 反应（根据 EORTC 指南）。其他终点包括基于实体瘤反应评价标准（RECIST）v1.1 的反应评估、动态对比增强（DCE）-MRI、弥散加权（DW）-MRI、安全性和转化研究（TR）。

结果

30 例患者被随机分配：25 例接受阿法替尼治疗，5 例接受对照组治疗。23 例符合条件的随机接受阿法替尼治疗的患者中，16 例（70%；95%CI：47%至 87%）患者有部分代谢 FDG-PET 反应（PMR）。5 例（22%；95%CI：8%至 44%）患者通过 RECISTv1.1 显示部分缓解。通过 DCE-MRI 和 DW-MRI 评估的反应与 PMR 或 RECIST 没有很强的相关性。1 例患者因 3 级腹泻（随后发生肾衰竭）和 24 天手术延迟而在接受阿法替尼治疗 11 天后停药。未报告与阿法替尼相关的 4 级毒性或手术合并症。TR 结果表明，在高 Cluster3-缺氧评分表达和 TP53 野生型的肿瘤中，PMR 更为常见。