1. www.OncologyEducation.ca Phase III study of first-line XELOX plus bevacizumab (BEV) for 6 cycles followed by CapeOX plus BEV or single agent (s/a) BEV as maintenance therapy in patients (pts) with metastatic colorectal cancer (mCRC) the MACRO trial Authors: Tabernero et al Review by Scott Berry Date posted: Aug 4 2010

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3. www.OncologyEducation.ca R CapeOx + Bevacizumab x 6 Cycles Then Continue CapeOx + Bevacizumab until progression First Line mCRC N= 480 Primary Outcome: PFS (non-inferiority) Study Design CapeOx + Bevacizumab x 6 Cycles Then Single Agent Bevacizumab until progression

4. www.OncologyEducation.ca Statistical analysis Non-inferiority design –Assuming 10 months as median PFS –Non-inferiority limit of 7.6 m (HR=1.32) –Alpha error = 0.025, one side –Power = 80%

5. www.OncologyEducation.ca RESULTS Continued CapeOx + Bev Single Agent Bev HR (95% CI) PFS (median, mos) 10.4 9.7 1.11 (0.89–1.37) OS (median, mos) 23.421.7 1.04 (0.81–1.32)

6. www.OncologyEducation.ca Gr 3/4 TOXICITY Continued CapeOx + Bev Gr 3/4 Single Agent Bev Gr 3/4 NEUROPATHY SENSORY 24.87.6 DIARRHEA10.913.9 HAND FOOT SKIN REACTION12.26.7 FATIGUE10.54.2 HYPERTENSION3.87.1 PROTEINURIA0.41.7 THROMBOSIS0.81.3 PERFORATION, GI0.80.4 BLEEDING0.4 OBSTRUCTION/GI.0.4 CARDIAC ISCHEMIA.0.4

7. www.OncologyEducation.ca STUDY COMMENTARY Study did not meet pre-specified HR limit for non-inferiority of PFS Discussant : given upper limit 95% CI for PFS = 1.37 study does not exclude potential PFS detriment of 3.7 mos for single agent bevacizumab Decreased neurotoxicity in single agent bev arm Based on this data, this maintenance strategy cannot be recommended