Targeting the epidermal growth factor receptor in addition to chemotherapy in patients with advanced pancreatic cancer: a systematic review and meta-analysis

Overexpression of epidermal growth factor receptors (EGFR) occurs in >90% of pancreatic ductal adenocarcinomas (PDACs) and is associated with a worse prognosis. A systematic review of electronic databases identified studies exploring the addition of EGFR-targeted treatment to chemotherapy in patients with locally advanced (LA)/metastatic PDAC. Efficacy, safety and tolerability of EGFR-targeted therapy were explored using meta-analysis of randomised controlled trials (RCTs). Meta-regression was utilised to explore factors associated with improved prognosis (all studies) and benefit from EGFR-targeted therapy (RCTs). Twenty-eight studies (7 RCTs and 21 cohort studies) comprising 3718 patients were included. The addition of EGFR-targeted treatment to chemotherapy did not improve progression-free (pooled hazard ratio [HR]:0.90, p=0.15) or overall survival (HR:0.94, p=0.18). EGFR-targeted therapy was associated with increased treatment-related deaths (pooled odds ratio [OR]:5.18, p=0.007), and Grade[G]3/4 rash (OR:4.82, p=0.03). There was a borderline significant increase in G3/4 diarrhoea (OR:1.75, p=0.06), but no effect on treatment discontinuation without progression (OR:0.87, p=0.25). Neither G3/4 rash nor diarrhoea were associated with increased survival benefit from EGFR-targeted therapy. The effect of EGFR-targeted therapy on OS appeared greater in studies with a greater proportion of LA rather than metastatic patients (R=-0.69, p<0.001). Further studies in unselected patients with advanced PDAC are not warranted. The benefit from EGFR inhibitors may be limited to patient subgroups not yet clearly defined.