Filippini Daria Maria, Sanchez Raphael, Bastien Etienne, Jacquin Nicolas, Paccapelo Alexandro, Nhy Caroline, Klijanienko Jerzy, Calugaru Valentin, Chilles Anne, Ghanem Wahib, Rougier Guillaume, Dubray Vautrin Antoine, Badois Nathalie, Lesnik Maria, Choussy Olivier, Sablin Marie Paule, Le Tourneau Christophe, Marret Grégoire
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant' Orsola-Malpighi Hospital, Pietro Albertoni Street, Bologna I-40138, Italy.
Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.
Ther Adv Med Oncol. 2025 Jun 30;17:17588359251337244. doi: 10.1177/17588359251337244. eCollection 2025.
Recent advances in understanding the biology of cancer have resulted in an extensive armamentarium of new therapeutic agents, most often tested on various tumor types at the earliest stages of drug development. However, the clinical impact of these therapies on patients with head and neck cancer (HNC) remains underexplored and requires further evaluation.
To investigate the clinical outcomes and toxicity profiles of patients with HNC enrolled in phase I trials (Ph1t) at a tertiary referral center over the last decade.
A retrospective cohort study was conducted, analyzing data from HNC patients enrolled in phase I trials at the Curie Institute between October 2011 and January 2024.
Data on baseline characteristics, hematologic biomarkers, and outcomes were extracted from medical records. Objective response rate (ORR) and Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were analyzed. A Cox model was used for the identification of prognostic factors.
One hundred and thirty patients were enrolled in Ph1t for recurrent/metastatic (R/M) setting (66.9%), including 20.8% of patients being treated with more than two lines of therapy, followed by locally advanced (LA) treated with radical surgery or exclusive chemo/radiotherapy (17.7%), neoadjuvant (10.0%), and adjuvant (5.4%) Ph1t. Patients were treated with immunotherapy (53.8%), targeted therapy (23.1%), bispecific antibody (8.5%), antibody-drug conjugate (4.6%), and other agents (10.0%). In 122 patients evaluable for response, ORR were 16.5%, 87.0%, and 92.3% in R/M, LA, and neoadjuvant Ph1t, respectively. Median PFS/OS rates were 2.0/8.3, 21.5/38.3, and 20.0/27.4 months in R/M, LA, and neoadjuvant Ph1t, respectively.At multivariable analysis, lower lymphocytes (HR = 0.144; 95% CI: 0.052-0.399; < 0.001) and lower albumin levels (HR = 0.922; 95% CI: 0.879-0.966; < 0.001) remained associated with poorer OS. Grade 3-4 adverse events were recorded in 27/130 patients (20.8%). The most frequent were hematologic and gastrointestinal disorders. No treatment-related deaths occurred.
HNC Ph1t show encouraging results in terms of early efficacy signals and safety profiles, emphasizing their value across a variety of clinical settings.
在癌症生物学认识方面的最新进展带来了大量新型治疗药物，这些药物大多在药物研发的最初阶段就针对各种肿瘤类型进行了测试。然而，这些疗法对头颈癌（HNC）患者的临床影响仍未得到充分探索，需要进一步评估。
调查过去十年在一家三级转诊中心参加I期试验（Ph1t）的HNC患者的临床结局和毒性特征。
进行了一项回顾性队列研究，分析了2011年10月至2024年1月期间在居里研究所参加I期试验的HNC患者的数据。
从病历中提取基线特征、血液生物标志物和结局数据。分析客观缓解率（ORR）以及无进展生存期（PFS）和总生存期（OS）的Kaplan-Meier估计值。使用Cox模型识别预后因素。
130例患者参加了复发/转移（R/M）情况下的Ph1t（66.9%），其中20.8%的患者接受了超过两线的治疗，其次是接受根治性手术或单纯化疗/放疗的局部晚期（LA）患者（17.7%）、新辅助治疗患者（10.0%）和辅助治疗患者（5.4%）。患者接受了免疫治疗（53.8%）、靶向治疗（23.1%）、双特异性抗体治疗（8.5%）、抗体药物偶联物治疗（4.6%）和其他药物治疗（10.0%）。在122例可评估缓解情况的患者中，R/M、LA和新辅助Ph1t的ORR分别为16.5%、87.0%和92.3%。R/M、LA和新辅助Ph1t的中位PFS/OS率分别为2.0/8.3、21.5/38.3和20.0/27.4个月。在多变量分析中，较低的淋巴细胞水平（HR = 0.144；95% CI：0.052 - 0.399；P < 0.001）和较低的白蛋白水平（HR = 0.922；95% CI：0.879 - 0.966；P < 0.001）仍然与较差的OS相关。27/130例患者（20.8%）记录到3 - 4级不良事件。最常见的是血液学和胃肠道疾病。未发生与治疗相关的死亡。
HNC的Ph1t在早期疗效信号和安全性方面显示出令人鼓舞的结果，强调了它们在各种临床环境中的价值。
