Outcomes of Epidermal Growth Factor Receptor Inhibitors in Locally Advanced and Metastatic Anal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence and limited systemic options in recurrent or metastatic disease. Although epidermal growth factor receptor (EGFR) inhibitors show activity in other squamous cancers, their role in ASCC remains unclear due to fragmented evidence. This systematic review and meta-analysis evaluated the efficacy and safety of EGFR inhibitors in adults with locally advanced or metastatic ASCC. PubMed/MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to December 2025 for studies of EGFR inhibitors in ASCC. Eligible designs included randomized trials, phase II studies, prospective or retrospective cohorts, and case series. Proportional meta-analyses were performed using fixed- or random-effects models according to heterogeneity. Twelve studies including 404 patients were analyzed. Median age ranged from 47 to 65 years, and both locally advanced and metastatic settings were represented. The EGFR inhibitors cetuximab and panitumumab were administered with chemoradiotherapy in locally advanced disease or with systemic therapy in metastatic or refractory settings. The pooled objective response rate was 52% (95% CI: 36-68; I²=84.2%, τ²=0.0518, p < 0.0001), with a complete response rate of 37% (95% CI: 15-61; I²=94.0%, τ²=0.1287, p < 0.0001). Median overall survival was 11.9 months and progression-free survival 4.5 months. Grade ≥ 3 adverse events occurred in 56% of patients; treatment discontinuation was infrequent (8%), and no treatment-related deaths were reported. EGFR inhibitors show a reproducible signal of activity in locally advanced and metastatic ASCC with manageable toxicity, though evidence is limited by nonrandomized designs and heterogeneity; prospective, biomarker-driven studies are needed.