Colon Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IV and Recurrent Colon Cancer Treatment
Based on these studies, bevacizumab can reasonably be added to either FOLFIRI or FOLFOX for patients undergoing first-line treatment of metastatic colorectal cancer. A major question was whether the use of bevacizumab after first-line therapy was warranted when bevacizumab was used as a component of first-line therapy. At the 2012 American Society of Clinical Oncology Annual Meeting, data was presented from a randomized, controlled trial. In the trial, 820 patients with metastatic colorectal cancer, after progressing on first-line chemotherapy that included bevacizumab, were randomly assigned to chemotherapy without bevacizumab or chemotherapy with bevacizumab. Patients who received bevacizumab experienced an improved OS compared with the patients who did not receive bevacizumab. Median OS was 11.2 months for patients who received bevacizumab plus chemotherapy and 9.8 months for patients who received chemotherapy without bevacizumab (HR, 0.81; 95% CI, 0.69–0.94; unstratified log-rank test, P = .0062). Median PFS was 5.7 months for patients who received bevacizumab plus chemotherapy and 4.1 months for those who received chemotherapy without bevacizumab (HR, 0.68; 95% CI, 0.59–0.78; unstratified log-rank test, P < .0001).][Level of evidence: 1iiA]
Aflibercept is a novel anti-VEGF molecule and has been evaluated as a component of second-line therapy in patients with metastatic colorectal cancer. In one trial, 1,226 patients were randomly assigned to receive aflibercept (4 mg/kg IV) or placebo every 2 weeks in combination with FOLFIRI. Patients who received aflibercept plus FOLFIRI had a significantly improved OS relative to placebo plus FOLFIRI (HR, 0.817; 95.34% CI, 0.713–0.937; P = .0032) with median survival times of 13.50 months versus 12.06 months, respectively. Aflibercept also significantly improved PFS (HR, 0.758; 95% CI, 0.661–0.869; P < .0001), with median PFS times of 6.90 months versus 4.67 months, respectively. On the basis of these results, the use of FOLFIRI plus aflibercept is an acceptable second-line regimen for patients previously treated with FOLFOX-based chemotherapy.[Level of evidence: 1A] Whether to continue bevacizumab or initiate aflibercept in second-line therapy has not been addressed as yet in any clinical trial, and there are no data available.
Cetuximab is a partially humanized monoclonal antibody against the epidermal growth factor receptor (EGFR). Because cetuximab affects tyrosine kinase signaling at the surface of the cell membrane, tumors with mutations causing activation of the pathway downstream of the EGFR, such as KRAS mutations, are not sensitive to its effects. The addition of cetuximab to multiagent chemotherapy improves survival in patients with colon cancers that lack a KRAS mutation (i.e., KRAS wild type). Importantly, patients with mutant KRAS tumors may experience worse outcome when cetuximab is added to multiagent chemotherapy regimens containing bevacizumab.