Epidermal growth factor receptor inhibitors in advanced cutaneous squamous cell carcinoma: A systematic review and meta‐analysis

Abstract Patients with advanced cutaneous squamous cell carcinoma (cSCC) who are not eligible for or who fail to respond to anti‐PD1 immunotherapy have few treatment options. Epidermal growth factor receptor (EGFR) inhibitors have been investigated as a therapeutic option for advanced cSCC; however, data are limited to small single‐arm trials or retrospective studies. A systematic review and meta‐analysis was conducted to PRISMA guidelines (CRD42023394300). Studies reporting on outcomes of EGFR inhibition in advanced cSCC were identified. Objective response rate (ORR), progression‐free survival (PFS), overall survival (OS) and adverse event (AE) rate were pooled using a random effects model and the inverse variance method. Twelve studies (six prospective, six retrospective) were identified, representing 324 patients. Pooled ORR was 26% (95% confidence interval [CI] 18–36), median PFS was 4.8 months (95% CI 3.9–6.6) and median OS was 11.7 months (95% CI 9.2–14.1). Any grade AEs occurred in 93% of patients (95% CI 85–97) while grade 3 and higher AEs occurred in 30% (95% CI 14–54). These results were similar between anti‐EGFR monoclonal antibodies (MAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors can be considered in patients with advanced cSCC who are contraindicated for or progress on first‐line anti‐PD1 immunotherapy. Future studies should evaluate their activity and safety following anti‐PD1, identify predictive biomarkers for their efficacy and explore combination approaches.