Department of Drug Development and Innovation (D3i), Institut Curie.
INSERM U900, Institut Curie, Paris-Saclay University, Paris, France.
Curr Opin Oncol. 2023 May 1;35(3):158-165. doi: 10.1097/CCO.0000000000000940. Epub 2023 Mar 14.
We review the window-of-opportunity clinical trials that have been reported in head and neck squamous cell carcinoma (HNSCC), and discuss their challenges.
Limited treatment options exist in HNSCC. Cetuximab, an mAb targeting epidermal growth factor receptor, and the PD-1 inhibitors nivolumab and pembrolizumab, are the only drugs that improved overall survival in the recurrent and/or metastatic setting. Both cetuximab and nivolumab improve overall survival by less than 3 months, potentially because of the lack of predictive biomarkers. The only validated predictive biomarker to date is protein ligand PD-L1 expression that predicts the efficacy of pembrolizumab in first-line, nonplatinum refractory recurrent and/or metastatic HNSCC. The identification of biomarkers of efficacy of new drugs is key to avoid administering toxic drugs to patients who will not benefit from them, and to expect increased drug efficacy in the biomarker-positive group of patients. One way of identifying such biomarkers are the window-of-opportunity trials in which drugs are given for a short period of time before the definitive treatment, with the aim to collect samples for translational research. These trials differ from neoadjuvant strategies where efficacy is the primary endpoint.
We show that these trials were safe and successful in identifying biomarkers.
我们回顾了头颈部鳞状细胞癌（HNSCC）的机会之窗临床试验，并讨论了它们所面临的挑战。
HNSCC 的治疗选择有限。西妥昔单抗是一种针对表皮生长因子受体的单克隆抗体，以及 PD-1 抑制剂纳武单抗和帕博利珠单抗，是唯一在复发性和/或转移性环境中提高总生存率的药物。西妥昔单抗和纳武单抗均使总生存率提高不到 3 个月，这可能是由于缺乏预测生物标志物。迄今为止唯一经过验证的预测生物标志物是蛋白配体 PD-L1 表达，它可预测帕博利珠单抗在一线、非铂类难治性复发性和/或转移性 HNSCC 中的疗效。确定新药疗效的生物标志物对于避免给不会从中受益的患者使用有毒药物，并期望在生物标志物阳性患者群体中提高药物疗效至关重要。一种识别此类生物标志物的方法是机会之窗试验，其中在确定性治疗之前短时间内给予药物，目的是为转化研究收集样本。这些试验与新辅助策略不同，后者的主要终点是疗效。
我们表明这些试验在识别生物标志物方面是安全且成功的。
