Neoadjuvant Nivolumab Plus Chemotherapy and Chemoradiation for Patients With HPV-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma
According to results from the phase 2 DEPEND trial, neoadjuvant nivolumab plus chemotherapy and response-stratified de-escalated chemoradiation demonstrated clinical promise among patients with human papillomavirus (HPV)-negative locally advanced head and neck squamous cell carcinoma.
“Neoadjuvant immunotherapy in [HPV]–negative locoregionally advanced head and neck squamous cell carcinoma appears promising, yet its role in nonsurgical treatment for head and neck cancer remains undefined,” stated Ari Rosenberg, MD, University of Chicago, Chicago, Illinois, and coauthors. “Neoadjuvant nivolumab plus chemotherapy followed by response-stratified de-escalated chemoradiation therapy … may improve treatment efficacy while reducing treatment-related toxic effects.”
In this nonrandomized study, 36 patients were assigned to receive 9 cycles of neoadjuvant nivolumab plus carboplatin and paclitaxel followed by either 66 Gy of de-escalated chemoradiation (for patients with ≥ 50% reduction; n = 19) or 70 to 75 Gy of standard chemoradiation (for patients with ≤ 50% reduction; n = 16). The primary end point was deep response rate. Key secondary end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.
At a median follow-up of 20 months, the deep response rate was 53% and the ORR was 86%. The 2-year PFS and OS rates were 66% among those who received de-escalated chemoradiation and 73% among those who received standard chemoradiotherapy. The most common treatment-emergent adverse events included mucositis, radiation dermatitis, and dry mouth.
“In this trial, neoadjuvant nivolumab plus chemotherapy followed by response-stratified chemoradiation in stage IVa/b nonvirally mediated head and neck cancer demonstrated favorable survival and less toxic effects among responders receiving response-adapted chemoradiation,” concluded Dr Rosenberg et al.
Source:
Rosenberg AJ, Juloori A, Jelinek MJ, et al. Neoadjuvant nivolumab plus chemotherapy followed by response-stratified chemoradiation therapy in HPV-negative head and neck cancer. JAMA Oncol. Published online: March 6, 2025. doi: 10.1001/jamaoncol.2025.0081
