Neoadjuvant chemotherapy with/without PD-1i in locally advanced laryngeal/hypopharyngeal cancer: A multicentered retrospective study.

6085 Background: The efficacy of adding programmed death-1 (PD-1) inhibitors to neoadjuvant chemotherapy (NACT) for improving survival in locally advanced laryngeal/hypopharyngeal carcinoma remains unclear. This study aimed to compare progression-free survival (PFS) between patients receiving NACT with or without a PD-1 inhibitor (NACT+PD-1i). Methods: This multicenter retrospective study enrolled 267 patients with T2-4N0-3M0 laryngeal/hypopharyngeal squamous cell carcinoma who received NACT with (n=165) or without (n=102) a PD-1 inhibitor, followed by definitive radiotherapy, between 2019 and 2024, from Fudan University Shanghai Cancer Center, Fujian Cancer Hospital and Sun Yat-sen University Cancer Center. The primary endpoint was PFS. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances. Results: The NACT+PD-1i group demonstrated significantly improved PFS versus NACT alone (median PFS: not reached vs. 33.0 months; hazard ratio [HR]=0.61, 95% confidence interval [CI]: 0.41–0.90; p=0.012). The 2-year PFS rates were 70.2% and 56.5%, respectively. This PFS benefit persisted after IPTW (p=0.012). PD-1 inhibition was an independent favorable factor for PFS in multivariable analysis (unadjusted, HR=0.54, p=0.005; IPTW-adjusted, HR= 0.63, p=0.040). Notably, the NACT+PD-1i group showed superior regional recurrence-free survival (RRFS) (2-year RRFS: 92.1% vs. 81.0%; HR=0.31, p=0.001) and higher objective response rate (ORR) (93.9% vs. 85.9%, p=0.027), particularly for cervical lymph nodes (94.2% vs. 81.6%, p=0.002). Achieving an ORR after neoadjuvant therapy was a strong predictor for improved outcome, either in unadjusted PFS (HR=0.40, p=0.0005) or in IPTW-adjusted PFS (HR=0.49, p=0.0005). Conclusions: In this real-world analysis, adding a PD-1 inhibitor to NACT significantly improved ORR and PFS in locally advanced laryngeal/hypopharyngeal carcinoma, supporting its further evaluation in neoadjuvant strategies.