Comparative review of KEYNOTE-689 and NIVOPOSTOP trials and their impact on perioperative immunotherapy in locally advanced head and neck cancer
Yoshinori Imamura, Masafumi Kanno, Shigeharu Fujieda
Abstract
AIM: To critically review the emerging evidence from two randomised trials-KEYNOTE-689 and NIVOPOSTOP-on perioperative immune checkpoint inhibition in resectable, locally advanced head and neck squamous cell carcinoma, and to elucidate how these positive results may redefine the current and future treatment paradigms. METHODS: We conducted a narrative review comparing the design, patient populations, treatment protocols, and outcomes of KEYNOTE-689 and NIVOPOSTOP. Data sources included ClinicalTrials.gov, presentations at major international oncology meetings, and peer-reviewed publications. RESULTS: KEYNOTE-689 adopted a broad perioperative strategy using pembrolizumab both pre- and postoperatively, with (chemo)radiotherapy administered based on pathological risk. NIVOPOSTOP employed a focused adjuvant approach, using nivolumab alongside postoperative chemoradiotherapy only in high-risk patients. Despite distinct strategies, both trials demonstrated significant improvements in event-free survival (KEYNOTE-689; hazard ratio 0.73; 95% confidence interval, 0.58-0.92) and disease-free survival (NIVOPOSTOP; hazard ratio 0.76; 95% confidence interval, 0.60-0.98). KEYNOTE-689 reduced distant recurrence, while NIVOPOSTOP improved loco-regional control. Although overall survival data remain immature, both show favourable trends. Treatment adherence and treatment-related serious adverse events were lower in KEYNOTE-689. CONCLUSIONS: Perioperative immune checkpoint inhibition is emerging as the first new standard in two decades for resectable locally advanced head and neck squamous cell carcinoma. KEYNOTE-689 highlights early immune priming, whereas NIVOPOSTOP offers a pragmatic, high-risk-targeted model with high compliance. Treatment selection should be tailored by recurrence risk, programmed death-ligand 1 expression, and multidisciplinary evaluation. Future priorities include refining patient selection and immune checkpoint blockade schedule, optimizing neoadjuvant regimens, implementing response-adapted de-escalation, and assessing cost-effectiveness.