Five-year follow-up of neoadjuvant chemoimmunotherapy in locally advanced head and neck squamous cell carcinoma.

6102 Background: Neoadjuvant chemoimmunotherapy has shown high rates of pathological response in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, its long-term survival outcomes, the predictive value of pathological complete response (pCR), and patterns of late failure remain unclear. Methods: In this single-arm phase II trial, 30 patients with resectable LA-HNSCC received three cycles of nab-paclitaxel (or docetaxel) plus cisplatin and camrelizumab, followed by surgery and adjuvant radiotherapy. The primary endpoint was pCR rate. With follow-up until January 2026, the median follow-up was 60 months. Analyses included overall survival (OS), recurrence patterns, and incidence of second primary tumors. Results: The pCR rate was 37.0% (10/27). Key Finding 1: This study represents the first report of 5-year long-term survival data for this regimen, with a 5-year OS rate of 76.7%. Key Finding 2: None of the patients who achieved pCR and completed adjuvant radiotherapy experienced local recurrence (0/7), whereas the recurrence rate was 33.3% (1/3) among those who did not receive radiotherapy, underscoring the role of radiotherapy even in pCR patients. Key Finding 3: Six patients (20%) developed second or third primary tumors during long-term follow-up (sites included larynx, esophagus, and lung), with incidence increasing over time. Key Finding 4: Two patients developed osteoradionecrosis of the jaw more than two years after radiotherapy, leading to malnutrition and subsequent death, highlighting the importance of long-term toxicity management. Conclusions: Neoadjuvant chemoimmunotherapy provides durable survival benefit in LA-HNSCC. pCR is associated with minimal local recurrence. However, with prolonged survival, the risk of second primary tumors becomes significant, and late radiation toxicities can impact outcomes. These findings emphasize the need for establishing lifelong surveillance protocols for multiple primary cancers and systematic management of late toxicities in this population. Clinical trial information: ChiCTR1900025303.