# PD1/PD-L1 Axis Blockers in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes

## TL;DR

This study reviews the effectiveness and safety of PD1/PD-L1 inhibitors in treating head and neck cancer, showing better survival and fewer side effects compared to standard treatments.

## Contribution

A systematic review and meta-analysis of randomized trials on PD1/PD-L1 inhibitors in head and neck squamous cell carcinoma.

## Key findings

- PD1/PD-L1 inhibitors improved overall survival in head and neck cancer patients compared to standard therapy.
- Treatment with PD1/PD-L1 inhibitors showed better duration of response and fewer severe side effects.
- Patients with PD-L1≥1% experienced significant survival benefits from PD1/PD-L1 inhibitors.

## Abstract

Cancers of the head and neck are common, and this review aimed to systematically analyze the safety and efficacy of anti-PD1/PD-L1 inhibitors (API) therapies in head and neck squamous cell carcinoma (HNSCC). This is a systematic review of randomized controlled trials (RCTs) showcasing the safety and efficacy of APIs in HNSCC. An online literature search of PubMed, Cochrane database, and ClinicalTrials.gov was conducted till May 31, 2024, to identify RCTs involving anti-PD1/PD-L1 therapies in oral cancer. The data were analyzed using Review Manager (RevMan) (Cochrane, London, United Kingdom), and the risk of bias was assessed for methodological quality. This study included nine RCTs with 3933 study participants. API treatment showed a significant improvement in overall survival (OS) compared to standard therapy in HNSCC (hazard ratio (HR) =0.85 (0.76,0.95), I2=26%, P=0.004). Even participants with PD-L1≥1%, treated with APIs, manifested substantial advancement of OS. Duration of response (DOR) was notably improved with API (HR= 0.31 (0.20, 0.50), I2=0%, P <0.00001) compared to standard therapy. Safety outcomes revealed comparatively reduced incidence of treatment-related adverse events and Grade 3/4 adverse effects when treated with APIs compared to standard therapy. In the era of emerging immunotherapy, APIs may be considered an alternative therapy in HNSCC, which could improve the OS, OS in patients with >1% PD-L1 expression, and DOR, as well as with a better safety profile as compared to chemotherapy and combination ICI. APIs pave the way for novel therapeutic strategies incorporating immune checkpoint inhibitors in HNSCC management.