Comparison of efficacy between 2 and 3 cycles of neoadjuvant immunotherapy combined with chemotherapy for LA HNSCC.

6101 Background: To compare efficacy, safety and long-term survival of 2 vs 3 cycles of neoadjuvant PD-1 inhibitor plus chemotherapy for LA HNSCC, providing evidence for optimizing treatment cycles. Methods: Retrospective analysis of LA HNSCC patients treated with the above neoadjuvant regimen at Beijing Tongren Hospital (Jan 2022-Dec 2024) was performed. Initially 76 (2-cycle) and 102 (3-cycle) cases were enrolled. Propensity score matching (1:1) balanced baseline differences, resulting in 65 cases per group. Chi-square, Kappa, Kaplan-Meier and Log-rank tests were used for comparisons, consistency analysis and survival assessment. Stratified analyses focused on HPV-negative and poorly differentiated subgroups. Results: After matching, 3-cycle group had higher ORR (95.4% vs 80.0%, P=0.008) and pCR rate (72.3% vs 55.4%, P=0.045). Subgroup analyses showed superior pCR in 3-cycle group for HPV-negative (68.9% vs 42.1%, P=0.014) and poorly differentiated (82.6% vs 35.7%, P=0.004) patients. Weak consistency existed between imaging and pathology (Kappa=0.176, P=0.044). Immune-related adverse events were more common in 3-cycle group (24.6% vs 10.8%, P=0.039). No significant 1-/2-year PFS/OS differences were noted, but 3-cycle group showed favorable numerical trend. Conclusions: Three cycles of the regimen significantly improve ORR and pCR in LA HNSCC, especially in HPV-negative and poorly differentiated subgroups. Despite higher immune-related adverse events, it is clinically preferable. Multi-dimensional evaluation is needed due to poor imaging-pathology consistency, with longer follow-up required for definitive prognosis assessment.