Efficacy of neoadjuvant pembrolizumab combined with paclitaxel and cisplatin in locally advanced oropharyngeal and hypopharyngeal squamous cell carcinoma: a retrospective study.

Objective: This retrospective study aims to evaluate the efficacy and safety of pembrolizumab combined with paclitaxel and cisplatin (ICI+TP) in the treatment of locally advanced oropharyngeal and hypopharyngeal squamous cell carcinoma (OPHSCC). Methods: Patients with locally advanced OPHSCC who received ICI+TP, cetuximab with paclitaxel-cisplatin (CET+TP), or paclitaxel-cisplatin alone (TP) were reviewed. Radiographic and pathological response rates, transoral surgery rates, and survival outcomes were assessed. Results: A total of 83 patients were enrolled in this study, with 23 subjected to ICI+TP, 31 to CET+TP, and 29 to TP. Compared with TP, ICI+TP yielded superior clinical outcomes: a higher objective response rate (ORR) (91.3% vs. 55.2%, p<0.05), greater transoral surgery feasibility (91.3% vs. 34.5%, p<0.05), lower tracheostomy incidence (26.1% vs. 79.3%, p<0.05). Among hypopharyngeal carcinoma patients, ICI+TP achieved an ORR of 100%, outperforming both CET+TP (62.5%) and TP (51.9%). The transoral surgery rate reached 89.5% (vs. 29.6% with TP, p<0.05) while tracheostomy requirements were reduced (21.1% vs. 85.2%, p<0.05). Notably, ICI+TP produced significantly higher primary tumor pathological complete response rates than CET+TP (57.9% vs. 20.8%, p<0.05). Median follow-up was 10 months for ICI+TP, 13 months for CET+TP, and 24 months for TP. Neither progression-free nor overall survival showed significant improvement among the three groups. Conclusion: In locally advanced OPHSCC, neoadjuvant pembrolizumab combined with paclitaxel and cisplatin showed a higher ORR and increased transoral surgery rates while preserving laryngeal function, with no increase in severe treatment-related adverse events, demonstrating favorable efficacy and safety profiles.