Neoadjuvant chemoimmunotherapy for locally advanced squamous cell carcinoma of the head and neck: Systematic review and meta-analysis

Neoadjuvant chemoimmunotherapy emerged as a promising treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, a comparison of clinical outcomes with neoadjuvant chemotherapy was lacking. To provide evidence supporting clinical decision-making for neoadjuvant chemoimmunotherapy in LA-SCCHN treatment. Literature was retrieved from PubMed, Web of Science, Embase, and the Cochrane Library for studies on the efficacy and safety of neoadjuvant chemoimmunotherapy and chemotherapy in LA-SCCHN published before August 10, 2024. The study was registered in the PROSPERO (CRD42024573816). A total of 28 clinical trials with 2021 patients were included. The neoadjuvant chemoimmunotherapy group had significantly higher pathologic complete response (pCR) (33 % vs. 18 %, P = 0.04) and partial response (PR) (65 % vs. 38 %, P < 0.01). No significant differences were found in overall survival (OS) (hazard ratio: 0.85, 95 % CI: 0.77-0.93) and progression-free survival (PFS) (hazard ratio: 0.72, 95 % CI: 0.61-0.86). Regarding safety outcomes, in the single-arm trials, grade 3-4 treatment-related adverse events (TRAEs) occurred in 14 % of the chemoimmunotherapy group and 13 % of the chemotherapy group, with grade 5 TRAEs at 0 % and 4 %, respectively, showing no significant difference (P = 0.80; P = 0.08). In both RCTs and non-RCT, chemoimmunotherapy had a higher Risk Ratio (RR) for grade 3-4 TRAEs (RR: 1.42, 95 % CI: 0.87-2.31). Neoadjuvant chemoimmunotherapy has shown promising efficacy and safety for LA-SCCHN, but further randomized trials are needed to confirm long-term survival benefits.