Response-Adapted Postoperative Therapy Following Neoadjuvant Chemoimmunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: a phase II trial

Abstract

Neoadjuvant chemo-immunotherapy (NACI) demonstrates promising efficacy in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), yet its effect on postoperative radiotherapy/chemoradiotherapy (PORT/POCRT) remains undefined. This open-label phase 2 study (NCT05476965) assessed NACI efficacy and its role in guiding adaptive PORT/POCRT. Primary endpoint was major pathologic response (MPR) rate (0-10% residual tumor). Secondary endpoints are overall survival (OS), disease-free survival (DFS), objective response rate (ORR), and adverse events. Thirty resectable stage III–IVB HNSCC patients received sintilimab plus chemotherapy, followed by surgery and response-adapted PORT/POCRT. Patients with MPR received low-dose PORT (0–54 Gy), while patients without MPR received standard PORT/POCRT. The MPR rate was 59.1% (38.7%-76.7%). The MPR with low-dose group showed higher 2-year OS (100% vs. 77.8%) and DFS (100% vs. 55.6%) with fewer radiotherapy-related adverse events than non-MPR with standard-dose group (all P < 0.05). Adaptive radiation de-escalation maintains survival while reducing toxicity, representing a new strategy for LA-HNSCC. Neoadjuvant chemo-immunotherapy has emerged as a promising approach for locally advanced head and neck squamous cell carcinoma (HNSCC), but its implications for postoperative treatment remain uncertain. This phase 2 study reports efficacy outcomes of response-adapted postoperative therapy following sintilimab plus paclitaxel and cisplatin in patients with resectable HNSCC.