Phase 2 trial of neoadjuvant nivolumab plus chemotherapy followed by response-stratified chemoradiation for HPV-negative head and neck cancer

Neoadjuvant immunotherapy in HPV-negative locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) appears promising, but its role in nonsurgical treatment is not yet clear. The phase 2 DEPEND trial, at the University of Chicago, IL, found that among 36 patients with stage IVa/b HPV-negative HNSCC, neoadjuvant nivolumab plus chemotherapy led to a deep response (≥ 50% tumor shrinkage) in 53% of patients, which met the statistical endpoint, while 86% achieved an objective response (≥ 30% tumor shrinkage). Patients with deep response received de-escalated chemoradiation therapy, with favorable survival outcomes and lower rates of acute toxic effects compared to standard chemoradiation therapy. The authors conclude that neoadjuvant nivolumab plus chemotherapy followed by response-adapted chemoradiation among patients with deep response led to promising outcomes.