# Efficacy and Safety of Different Neoadjuvant Treatment Regimens in Locally Advanced Squamous Head and Neck Cancer

## TL;DR

This study compares different treatment options for advanced head and neck cancer, finding that hyperthermia plus chemotherapy and immunotherapy plus chemotherapy are most effective but may have safety concerns.

## Contribution

The study provides a network meta-analysis comparing the efficacy and safety of various neoadjuvant therapies for locally advanced head and neck squamous cell carcinoma.

## Key findings

- Hyperthermia + chemotherapy showed the best objective response rate and overall survival.
- Immunotherapy + chemotherapy outperformed most other regimens in objective response rate and progression-free survival.
- Hyperthermia + chemotherapy and TPF had the poorest safety profiles.

## Abstract

Head and neck squamous cell carcinoma (HNSCC), which constitutes approximately 90% of all head and neck cancers, represents a significant global health burden. A concerning trend is the rising incidence, particularly among younger populations, which has been partly attributed to human papillomavirus (HPV) infection. While treatment outcomes are favorable for early‐stage disease, approximately 60% of patients are diagnosed with locally advanced HNSCC (LA‐HNSCC), for whom prognosis remains suboptimal. Induction chemotherapy, such as the TPF regimen, is often used to reduce tumor burden but is limited by substantial toxicity. Currently, no global consensus exists on the optimal neoadjuvant approach for LA‐HNSCC. This network meta‐analysis aims to comprehensively compare the efficacy and safety of available neoadjuvant therapies for LA‐HNSCC, excluding nasopharyngeal carcinoma due to distinct treatment paradigms, in order to inform clinical decision‐making.

To compare the efficacy and safety of different neoadjuvant treatment options in locally advanced head and neck squamous cell carcinoma (LA‐HNSCC).

We conducted a comprehensive literature search across four major databases (PubMed, Web of Science [WOS], Embase, and Cochrane Library) from their inception through August 2024. The primary outcome measures included objective response rate (ORR), overall survival (OS), progression‐free survival (PFS), and serious adverse events (SAEs). This analysis included 23 studies (19 randomized controlled trials [RCTs] and 4 non‐randomized studies [NRS]) involving 4052 patients. Network meta‐analysis (NMA) revealed the following findings: Regarding efficacy, hyperthermia + chemotherapy demonstrated superior outcomes in both ORR and OS, followed by immunotherapy + chemotherapy. Hyperthermia + chemotherapy showed significantly better ORR compared to targeted therapy + chemotherapy, TP, PF, T, and single‐agent immunotherapy (p < 0.05). Similarly, immunotherapy + chemotherapy outperformed all other therapies except hyperthermia + chemotherapy in ORR (p < 0.05). For OS, both hyperthermia + chemotherapy and TPF were significantly more effective than PF and TP (p < 0.05). In PFS, immunotherapy + chemotherapy showed the best results, followed by targeted therapy + chemotherapy, with immunotherapy + chemotherapy being significantly superior to PF (p < 0.05). Regarding safety, hyperthermia + chemotherapy showed the poorest safety profile, followed by TPF. Specifically, T and TP demonstrated significantly better safety than hyperthermia + Chemotherapyy (p < 0.05).

In the neoadjuvant treatment of LA‐HNSCC, both hyperthermia + chemotherapy and immunotherapy + chemotherapy regimens have demonstrated promising therapeutic efficacy; however, their safety profiles require further comprehensive evaluation.

Trial Registration: PROSPERO CRD42024571174