A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC): In-Depth Analysis of Nintendanib Arm from the KCSG HN 15-16 TRIUMPH Trial

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 NGS-based, matching genomic profiles. Patients whose tumors harbor 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 Oct 2017 and Aug 2020, 207 were enrolled in the TRIUMPH study, and 8 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 PR 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 small number of patients due to slow accrual in this study, further studies with large cohort are warranted for statistical power.