AGITG 2013* Meta-analysis of overall survival impact of biological therapy in relapsed metastatic colorectal cancer (#20)
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 overall survival (OS) for patients with mCRC beyond first-line therapy.
Methods: We searched MEDLINE, EMBASE, The Cochrane Library, along with the Proceedings of the American Society of Clinical Oncology (ASCO) ASCO Gastrointestinal Cancers Symposium and European Society for Medical Oncology meetings for randomised studies of relapsed mCRC comparing 1) chemotherapy with biologic agent(s) to chemotherapy alone and 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. Relevant data were pooled for meta-analysis using generic inverse-variance methodology. We limited analysis to the clinically available agents - targeting VEGF and EGFR pathways.
Results: We identified 11 studies evaluating 7145 patients. An overall survival benefit was not demonstrated for second-line EGFR inhibitors (3 studies, HR 0.95 [95% CI 0.86-1.05]; KRAS WT only). However an OS benefit was demonstrated for third-line EGFR inhibitors (2 studies, HR 0.75 [95% 0.61-0.92; KRAS WT only), anti-VEGF agents (4 studies, HR 0.79 [95% CI 0.73-0.86]) and VEGFR Tyrosine Kinase Inhibitors (TKI) (2 studies, HR 0.83 [95% CI 0.73-0.94]).
Conclusion: The use of biologic agents beyond the first-line setting in mCRC can result in a benefit for overall survival. This benefit is evident with third-line EGFR inhibitors, second line anti-VEGF agents, and VEGFR TKI used third line and beyond, but not second line EGFR inhibitors. Further analysis of this data set for progression-free survival, toxicity and response rate will also inform opinion regarding clinical utility.
