Background: Biological therapies used in treatment of metastatic colorectal cancer (mCRC) are costly and there is ongoing debate about their contribution to management. We examined the impact of biological therapy on progression-free survival for patients with mCRC beyond first-line therapy.

Methods: We searched MEDLINE, EMBASE, The Cochrane Library, Proceedings of the American Society of Clinical Oncology (ASCO) ASCO Gastrointestinal Cancers Symposium and European Society for Medical Oncology meetings for randomised phase II/III studies in relapsed mCRC in two categories: 1) comparing chemotherapy with biologic agent(s) to chemotherapy alone; 2) biologic therapy alone compared with no active therapy. We extracted data on study design, participants, interventions and outcomes.  Study quality was assessed using the MERGE criteria. The studies were pooled for meta-analysis using generic inverse-variance methodology. Analysis was limited to the clinically available agents targeting VEGF and EGFR pathways.

Results: We identified 11 studies evaluating 7145 patients. A progression-free survival benefit was demonstrated for second-line EGFR inhibitors (3 studies, HR 0.72 [95% CI 0.65-0.78]), third-line EGFR inhibitors (2 studies, HR 0.42 [95% 0.35-0.52), VEGF agents (4 studies, HR 0.69 [95% CI 0.63-0.75]) and VEGFR tyrosine kinase inhibitors (TKI) (2 studies, HR 0.60 [95% CI 0.54-0.67]).

Conclusion: The use of biologic agents beyond the first-line setting in mCRC results in a benefit to progression-free survival. This benefit is evident with EGFR agents (in second- and third-line settings), anti-VEGF agents (second line) and VEGFR TKI (third line and beyond). Further analysis of this dataset for overall survival, toxicity and response rate will also inform opinion regarding clinical utility.