10 Background: Anal squamous cell carcinoma (ASCC) is a rare malignancy with limited systemic options. Epidermal growth factor receptor (EGFR) inhibitors have shown activity in other squamous cancers, but their role in ASCC remains unclear. We performed a systematic review and meta-analysis to evaluate their efficacy and safety in locally advanced and metastatic ASCC. Methods: Following PRISMA guidelines, we searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through June 2025 for studies with adults (≥18 years) with histologically confirmed ASCC treated with EGFR inhibitors. Thirteen eligible studies were included. Outcomes included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events (AEs). Random- or fixed-effects models were applied according to heterogeneity (I²>50%). Study quality was assessed using Joanna Briggs Institute tools. Results: Thirteen studies encompassing 404 patients were included. The EGFR inhibitors evaluated were cetuximab and panitumumab. Six studies examined first-line use in locally advanced disease, and the remainder assessed second-line or refractory metastatic ASCC. Gender distribution was 64% female and 36% male, with median age across studies ranging from 47 to 65 years. The pooled ORR was 52% (95% CI, 36–68; I²=84.2%), including complete response 37% (95% CI, 15–61; n=312) and partial response 20% (95% CI, 13–27; n=148). Median OS across four studies was 11.9 months (95% CI, 8.5–16.7). Lowest reported 1-year OS: 10%, and highest reported 3-year OS: 83%. Median PFS was 4.5 months (95% CI, 3.7–5.5), with 3-year PFS of 69% (95% CI, 59–77; n=106). Grade ≥3 toxicities were observed in 56% (95% CI, 27–82; n=368). The most frequent were diarrhea 49% 95% CI, 18–81, neutropenia 40% 95% CI, 21–62, and dehydration 29% 95% CI, 22–39. The reported treatment related-related mortality was 0% with pooled discontinuation occurring in 8% (95% CI, 2–17; n=324). Conclusions: EGFR inhibitors show promising activity in ASCC, with good efficacy and acceptable toxicity. These findings support further prospective evaluation, particularly in metastatic or refractory disease, and highlight the need for predictive biomarkers to guide patient selection. Further Randomized trials are essential to guide evidence-based adoption.
Mannan et al. (Sat,) studied this question.