Second-Line Therapy for Advanced Colorectal Cancer: EGFR vs. Continuation of VEGF Inhibition

Purpose of Review

We review second-line biological therapies for metastatic colorectal cancer (mCRC), including their mechanisms of action, adverse events, survival outcomes, optimal chemotherapy combinations, and sequencing of agents.

Recent Findings

The advent of biological therapeutics targeting vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways has enhanced the benefits afforded by the plethora of chemotherapeutic agents for patients with mCRC over the past 10 years, nearly tripling the median OS. Individual biomarkers predicting prognosis and response to VEGF vs. EGFR therapy have been identified. For patients who progress on first-line VEGF therapy, evidence suggests that continued VEGF inhibition may be as efficacious as changing to EGFR therapy with less adverse effects. However, for patients who progress after first-line EGFR therapy, early studies suggest changing to agents targeting the VEGF pathway.

Summary

Biological options for patients with mCRC who progressed on first-line concomitant chemotherapy and biologic therapy depend on individual tumor characteristics and choice of first-line therapy. Future research should focus on prognostic and predictive biomarkers to better inform choice of first-line and sequential therapy beyond progression.