Targeting the epidermal growth factor receptor (EGFR) in addition to chemotherapy in patients (pts) with advanced pancreas cancer: a systematic review and meta-analysis

Background: Overexpression of EGFR occurs in more than 90% of pancreatic cancers and is associated with a worse prognosis. The benefit of adding EGFR-targeted agents to chemotherapy in the advanced setting is unclear.Methods: A systematic review of electronic databases identified studies exploring the addition of EGFR-targeted treatment to chemotherapy in pts with locally advanced/metastatic pancreas cancer. Efficacy (overall survival [OS] and progression-free survival [PFS]), safety and tolerability (treatment-related death, treatment discontinuation without progression and grade (G) 3/4 adverse events) of EGFR-targeted therapy were explored using meta-analysis of randomized trials (RCTs). Meta-regression was utilized to explore factors associated with improved prognosis (all studies) and increased benefit from EGFR-targeted therapy (RCTs). Results: Twenty-eight studies comprising 3718 pts (69% metastatic) were included. Among these were 7 RCTs and 21 cohort studies. Addition of EGFR-targeted treatment to chemotherapy did not improve OS (pooled hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87-1.03, p=0.18) or PFS (pooled HR 0.90, 95% CI 0.78-1.04). EGFR-targeted therapy was associated with increased risk of treatment-related death (pooled odds ratio [OR] 5.18, 95% CI 1.58-16.97, p=0.007), and G 3/4 rash (OR 4.82, 95% CI 1.18-19.69, p=0.03). There was a near-significant increase in G 3/4 diarrhea (OR 1.75, 95% CI 0.97-3.15, p=0.06), but no effect on treatment discontinuation without progression (OR 0.87, 95% CI 0.68-1.10, p=0.25). Patients with kras mutations had worse OS (R=-0.88, p