Divison of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
Cancer Res Treat. 2024 Jan;56(1):37-47. doi: 10.4143/crt.2023.433. Epub 2023 Jul 20.
Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.
The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)-based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.
Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.
Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.
由于复发性和转移性头颈部鳞状细胞癌（HNSCC）的预后不佳，因此需要采用精准肿瘤学方法。我们对铂类耐药的 HNSCC（KCSG-TRIUMPH）患者进行了基于基因组谱的伞式试验。在此，我们报告了当前试验中尼达尼布组（第 3 组）的深入报告。
TRIUMPH 研究是一项多中心、开放标签、单臂 2 期试验，根据基于下一代测序（NGS）的匹配基因组谱将患者分配到治疗组。肿瘤中存在成纤维细胞生长因子受体（FGFR）改变的患者被纳入尼达尼布组（第 3 组），作为 TRIUMPH 研究的一部分。主要终点是总缓解率（ORR），次要终点包括总生存期（OS）、无进展生存期（PFS）、安全性和生物标志物分析。
2017 年 10 月至 2020 年 8 月期间，共有 207 例患者入组 TRIUMPH 研究，其中 8 例入组尼达尼布组。ORR 和疾病控制率分别为 42.9%和 57.1%。中位 PFS 为 5.6 个月，中位缓解持续时间为 9.1 个月。中位 OS 为 11.1 个月。1 例患者的部分缓解持续时间为 36 个月。总体而言，毒性谱是可以管理的。
尼达尼布单药在 FGFR 突变的复发性或转移性 HNSCC 患者中显示出显著疗效，且毒性谱可耐受。该研究的结果为常规 NGS 筛查和 FGFR 靶向治疗提供了依据。由于本研究入组速度较慢，患者人数较少，因此需要进一步的研究以获得更大的队列进行统计学分析。
