Angiogenesis leads to the growth, progression, and metastases of a variety of solid tumors, including metastatic colorectal cancer (mCRC), involving particularly the family of vascular endothelial growth factors (VEGF) and their receptors (VEGFR). Several anti-angiogenic inhibitors are already registered for mCRC therapy: bevacizumab, aflibercept, ramucirumab, regorafenib. Nintedanib is a new triple angiokinase oral inhibitor that potently blocks the proangiogenic pathways mediated by VEGFR, platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). Areas covered: The current state-of-the-art of anti-angiogenic inhibitors employed in the treatment mCRC patients, and in particular the role of nintedanib in this setting, is reviewed and discussed here. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken. Expert opinion: In first-line therapy, a phase II randomized trial showed that nintedanib plus chemotherapy was not inferior to the bevacizumab-based regimen. In heavily pretreated mCRC patients nintedanib improved some outcomes. During the natural history of mCRC resistances to anti-angiogenic therapies can set in and in this context, nintedanib, due to its triple inhibition, might play a role in compensatory angiogenesis overcoming the resistance developed due to VEGF directed therapy.
Keywords: Aflibercept; angiogenesis; bevacizumab; colorectal cancer; mCRC; nintedanib; ramucirumab; regorafenib.