Safety and Efficacy of Vismodegib and Sonidegib in Advanced Basal Cell Carcinoma of the Head and Neck: A Systematic Review and Meta‐Analysis

ABSTRACT Importance Basal cell carcinoma (BCC) is the most prevalent malignancy globally, with 75% occurring in the head and neck. Hedgehog pathway inhibitors (HHIs) may provide a treatment for locally advanced BCC (laBCC) and metastatic BCC (mBCC) of the head and neck. Objective This systematic review and meta‐analysis aimed to evaluate the safety and efficacy of these treatments specifically in the head and neck region. Data Sources An electronic database search was conducted in June 2024 across Embase, MEDLINE, CINAHL, and ClinicalTrials.gov . There were no date limits applied, with search constraints consisting of the English language. Study Selection Included were studies involving adults with confirmed laBCC or mBCC of the head and neck treated with either vismodegib or sonidegib, with histological or radiological confirmation. Studies were excluded if they involved concurrent treatments or lacked quantitative measures. After full text review was completed, there were 17 studies for inclusion. Data Extraction and Synthesis This systematic review and meta‐analysis were conducted in accordance with PRISMA guidelines using two independent observers. Data extraction was performed using a standardized Microsoft Excel Form. Statistical analyses were conducted using meta‐analysis software on jamovi using a random effects model. Main Outcome(s) and Measure(s) This study initially aimed to investigate both systemic immunotherapies and targeted therapies, but no articles were identified for systemic immunotherapies for laBCC or mBCC of the head and neck region. Thus, the sole focus of this article became targeted therapies. Primary outcomes assessed were overall response rate (ORR), complete response (CR), and partial response (PR), alongside the prevalence of adverse effects. Findings Seventeen studies involving 522 patients were analyzed, revealing a pooled ORR of 84.2% (95% CI : 77.1–91.3), CR of 33.8%, and PR of 47.7%. Common adverse effects included muscle spasms, dysgeusia, and fatigue, with a discontinuation rate of 13.2% due to adverse events. Conclusions and Relevance This systematic review and meta‐analysis demonstrated a high efficacy of vismodegib and sonidegib for treating advanced BCCs in the head and neck region, suggesting a viable option when surgery is not feasible. Further high‐quality research is necessary to optimize treatment outcomes for this patient population.