Single-center phase 2 trial of neoadjuvant nivolumab plus chemotherapy followed by response-adapted therapy for HPV+ OPC

Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in HPV-positive oropharyngeal cancer (HPV⁺ OPC) remains undefined. The phase 2 OPTIMA II trial at the University of Chicago evaluated neoadjuvant nivolumab plus chemotherapy followed by response-adapted locoregional therapy for locoregionally advanced HPV⁺ OPC. This trial of 73 patients demonstrated a deep response (≥ 50% tumor shrinkage) in 70.8% of evaluable patients. This response led to reduced local treatment for 86% of patients, excellent 2-year survival, and improved functional outcomes. Moreover, the expression of PD-L1 and clearance of circulating tumor HPV-DNA were associated with improved progression-free survival. The authors conclude that neoadjuvant nivolumab with chemotherapy followed by response-adapted treatment can provide excellent overall survival and functional outcomes, including in patients with high-risk HPV⁺ OPC.