Multicenter Prospective Phase II Study of Induction Therapy With Pembrolizumab, Cisplatin, and Fluorouracil in Patients With Locally Advanced Head and Neck Cancer.

BackgroundThe approved induction chemotherapy regimen with docetaxel, cisplatin, and 5-fluorouracil is associated with a high risk of severe toxicity, which may compromise the feasibility of subsequent chemoradiation. Safer and more effective induction strategies are needed for patients with unresectable locally advanced head and neck squamous cell carcinoma (HNSCC).MethodsWe aimed to evaluate the feasibility, efficacy, and safety of induction immunochemotherapy followed by (chemo)radiation in patients with unresectable locally advanced HNSCC. In this prospective, multicenter, non-randomized phase II trial, patients with PD-L1-positive (Combined Positive Score ≥1) locally advanced squamous cell carcinoma of the oropharynx, larynx, or hypopharynx and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 received three 21-day cycles of pembrolizumab, cisplatin, and 5-fluorouracil, followed by chemoradiotherapy or radiotherapy in the absence of disease progression.ResultsAmong 120 enrolled patients, 116 were evaluable for response. The objective response rate after induction therapy was 62.9%, including 16.4% complete responses. After a median follow-up of 26 months, the 2-year PFS and OS rates were 53.0% and 65.1%, respectively. Grade 3-4 adverse events occurred in 30.8% of patients, with neutropenia reported in 23.3% and febrile neutropenia in 1.7%. Immune-related events were infrequent and mild (skin rash: 1.7%; hypothyroidism: 0.8%). No treatment-related deaths occurred.ConclusionsInduction immunochemotherapy with pembrolizumab, cisplatin, and fluorouracil demonstrated encouraging efficacy, manageable toxicity, and high transition and completion rates of chemoradiation. These findings should be considered hypothesis-generating rather than practice-changing and require confirmation in a randomized trial.