Perioperative or adjuvant PD-1/PD-L1 blockade with curative-intent multimodality therapy for locally advanced head and neck squamous cell carcinoma: A systematic review and meta-analysis of randomized trials.

e18074 Background: Multiple phase III trials have evaluated the addition of perioperative or adjuvant/postoperative PD-1/PD-L1 blockade to curative-intent multimodality therapy in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), yielding heterogeneous results across treatment strategies. This study aims to assess the efficacy and safety of immune checkpoint inhibitors in LA-HNSCC. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from inception through January 2026 for randomized controlled trials in LA-HNSCC comparing standard curative-intent multimodality therapy with perioperative (neoadjuvant ± adjuvant) or adjuvant/postoperative PD-1/PD-L1 blockade (including maintenance after definitive therapy) versus standard therapy alone; trials evaluating concurrent PD-1/PD-L1 blockade during definitive chemoradiation were excluded. The primary outcome was time-to-event efficacy, pooling event-free survival and disease-free survival as hazard ratios (HRs). Secondary outcomes included treatment-related serious adverse events and treatment-related deaths (grade 5 events). Results: Three phase III randomized trials were included (n=1,786). Pooled analysis demonstrated improved event-free/disease-free survival with checkpoint inhibition: HR 0.79 (95% CI 0.68-0.91, I²=0%). Treatment-related serious adverse events were more frequent in the checkpoint inhibitors group RR 1.79 (95% CI 1.43-2.24, I²=0%). Rates of treatment-related deaths (grade 5 events) were similar between the two groups, RR 1.90 (95% CI 0.50-7.14, I²=0). Conclusions: The addition of perioperative or adjuvant/postoperative PD-1/PD-L1 blockade to curative-intent multimodality therapy in LA-HNSCC was associated with a significant improvement in event-free/disease-free survival. Safety was characterized by higher rates of treatment-related serious adverse events, with no meaningful increase in treatment-related deaths. These findings support immune checkpoint inhibition as an effective adjunct to curative-intent multimodality treatment strategies in LA-HNSCC. Data summary table with event counts for each outcome. Trial EFS/DFS (events) (ICI vs Control) Serious treatment-related AEs(ICI vs Control) Treatment-related deaths(ICI vs Control) KEYNOTE-689 136/363 vs 159/351 69/361 vs 33/315 4/361 vs 1/315 NIVOPOST-OP (GORTEC 2018-01) 112/332 vs 140/334 104/312 vs 59/306 2/312 vs 2/306 IMvoke010 89/203 vs 92/203 7/202 vs 1/203 1/202 vs 0/203 Total 337/898 vs 391/888 180/875 vs 93/824 7/875 vs 3/824