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Update on Anti-Angiogenesis Therapy in Colorectal Cancer
Kristen K Ciombor1, Richard M Goldberg1
1Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH.
Abstract:
Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen. The multikinase inhibitor regorafenib is modestly effective in the refractory colorectal cancer setting but confers significant toxicity. Ramucirumab, an anti-vascular endothelial growth factor receptor 2 molecule, has efficacy in combination with 5-fluorouracil, leucovorin and irinotecan after disease progression on a first-line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. Questions regarding optimal treatment setting, predictive biomarkers of response, and cost effectiveness of these anti-angiogenic agents and others are as yet unanswered.
Insights
Anti-angiogenic agents like bevacizumab and ramucirumab show efficacy in treating metastatic colorectal cancer. However, optimal use, biomarkers, and cost-effectiveness require further investigation for these crucial cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Angiogenesis is vital for colorectal cancer growth and proliferation.
- Anti-angiogenic agents are a key therapeutic strategy in colorectal cancer treatment.
- Several agents targeting angiogenesis have been developed and approved.
Purpose of the Study:
- To review the safety and efficacy of anti-angiogenic agents in colorectal cancer.
- To discuss the current landscape of approved anti-angiogenic therapies.
- To identify unanswered questions regarding the optimal use of these agents.
Main Methods:
- Literature review of clinical trials and studies on anti-angiogenic agents.
- Analysis of efficacy and safety data for bevacizumab, aflibercept, regorafenib, and ramucirumab.
- Discussion of treatment settings, biomarkers, and cost-effectiveness.
Main Results:
- Bevacizumab is effective in first-line and later settings for metastatic colorectal cancer.
- Aflibercept is approved for patients progressing on oxaliplatin-based chemotherapy.
- Regorafenib shows modest efficacy in refractory settings with significant toxicity.
- Ramucirumab is effective after progression on first-line therapy.
Conclusions:
- Anti-angiogenic agents have demonstrated value in colorectal cancer treatment.
- Key questions remain regarding optimal treatment sequencing and patient selection.
- Further research is needed on predictive biomarkers and cost-effectiveness.
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