Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France; Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, Università di Bologna, Bologna, Italy.
Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.
Chin Clin Oncol. 2024 Oct;13(5):73. doi: 10.21037/cco-24-33. Epub 2024 Sep 27.
The conventional method of drug development in oncology typically progresses through phase I, phase II and randomized phase III trials. Nevertheless, some recent drug approvals for head and neck cancer (HNC) relied on findings from single-arm phase II trials. This underscores the significance of disease-specific phase I trials as a crucial step in exploring new drugs for HNC patients. The purpose of this review is to present the currently available data of phase I clinical trials conducted in HNC and to provide an overview of ongoing therapeutic trends in HNC.
We performed a scoping review of phase I trials evaluating single-agent treatments specifically designed for HNC patients. The PubMed database was searched using "(phase I) AND (head and neck)". To ensure exhaustiveness, we also performed a search from the American Society of Clinical Oncology, European Society for Medical Oncology and American Association for Cancer Research websites.
We screened 1,134 articles and selected 29 trials that met eligibility criteria, published between 1994 and 2023, for a total of 741 patients. Twenty-one trials comprised patients with different sites of HNSCC and only 8 trials (27%) focused on a specified subsite of head and neck. Most of trials investigated treatments in recurrent/metastatic (R/M) settings (86%). Immunotherapeutic agents were the most examined followed by targeted agents, cytotoxic drugs and "others" including a nanoparticle, a therapeutic gene, a fusion protein and a modulator of gene expression. Among trials reporting activity for R/M head and neck patients (n=23), the global median overall response rate (ORR) was 12% and four trials (17%) did not report any response. The incidence of grade 3/4 treatment-related adverse events (TRAEs) was low (7%). However, in seven trials safety results are not clearly assessable from the published data.
Phase I trials of single agents designed for head and neck patients were generally safe but with a low ORR. Future development of new drugs dedicated for HNC patients that can more accurately reflect the heterogeneity of HNC and provide more detailed subgroup analyses is warranted.
肿瘤学中传统的药物开发方法通常经历 I 期、II 期和随机 III 期试验。然而，最近一些头颈部癌症（HNC）的药物批准依赖于单臂 II 期试验的结果。这突显了疾病特异性 I 期试验作为探索 HNC 患者新药的关键步骤的重要性。本综述的目的是介绍目前在 HNC 中进行的 I 期临床试验的现有数据，并概述 HNC 中正在进行的治疗趋势。
我们对专门针对 HNC 患者的单药治疗的 I 期临床试验进行了范围界定审查。使用“（I 期）和（头颈部）”在 PubMed 数据库中进行搜索。为了确保全面性，我们还从美国临床肿瘤学会、欧洲肿瘤内科学会和美国癌症研究协会的网站上进行了搜索。
我们筛选了 1134 篇文章，选择了 29 项符合入选标准的试验，共纳入 741 例患者，这些试验发表于 1994 年至 2023 年之间。21 项试验包括不同部位的 HNSCC 患者，只有 8 项试验（27%）专注于头颈部的特定亚部位。大多数试验在复发/转移性（R/M）环境中研究治疗方法（86%）。免疫治疗药物是最受关注的，其次是靶向药物、细胞毒性药物和“其他”药物，包括纳米颗粒、治疗基因、融合蛋白和基因表达调节剂。在报告 R/M 头颈部患者活性的 23 项试验中（n=23），全球中位总缓解率（ORR）为 12%，4 项试验（17%）未报告任何缓解。3/4 级治疗相关不良事件（TRAEs）的发生率较低（7%）。然而，在 7 项试验中，从已发表的数据中无法清楚地评估安全性结果。
专门针对头颈部患者的单药 I 期试验通常是安全的，但 ORR 较低。需要为 HNC 患者开发新的药物，这些药物能够更准确地反映 HNC 的异质性，并提供更详细的亚组分析。
