Antiangiogenic Therapy in Metastatic Colorectal Cancer

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Following four to six months of treatment with chemotherapy, a male patient with metastatic colorectal cancer (mCRC) received maintenance capecitabine plus bevacizumab for 8 months. After this point, the patient began to progress, and continued to have residual neuropathy, explains moderator John L. Marshall, MD.

The VELOUR study examined aflibercept in predominantly a second-line treatment scenario, notes Fadi Braiteh, MD, CPI. The study was primarily international, although 28% of patients enrolled were within the United States. Overall, the study demonstrated that aflibercept significantly extended survival by 1.4 months for patients with mCRC, resulting in FDA approval for the medication.

Furthermore, Braiteh notes, in the study, approximately a third of patients received first-line bevacizumab. For these patients, the survival advantage was more pronounced at 17.9 months compared to 12.8 months. However, this advantage may attributable to the efficacy of treatments in the United States, which is primarily the only location where bevacizumab is a standard first-line treatment. An examination of progression-free survival and object response rates in the North American population reveals more consistent findings.

An intriguing aspect of the VELOUR trial was the long-term follow-up of overall survival, Braiteh suggests. In general, the hazard ratio for survival continued to improve for more than a year-and-a-half following the initiation of treatment.

In addition to the VELOUR study, the TML study examined the efficacy of continuing bevacizumab plus the opposite chemotherapy regimen used in the first-line setting, notes Alan P. Venook, MD. This trial demonstrated a clear benefit for patients receiving continued treatment with bevacizumab in the second-line setting. However, this trial raised a few question, specifically regarding a possible downside to stopping treatment with angiogenesis inhibition, even for surgery, believes Venook.

Further examining the second-line treatment of patients, the phase III EAGLE study examined FOLFIRI plus bevacizumab at either a 5 mg/kg or 10 mg/kg dose in patients with mCRC who progressed on first-line bevacizumab plus an oxaliplatin-based therapy, explains Axel Grothey, MD. The study enrolled 387 patients, which is large for this type of trial, Grothey believes. Overall, the primary endpoint of progression-free survival was similar in both arms.

These results were unexpected when looking at the BRiTE registry, where most patients had received bevacizumab at 5 mg/kg, Grothey notes. It is possible that when a price was determined for aflibercept that it was meant to match the 10 mg/kg price of bevacizumab, Grothey suggests. As a result, aflibercept initially cost twice as much as bevacizumab to administer, since the 5 mg/kg dose of bevacizumab is more commonly used.