title: Second-line angiogenesis inhibition in metastatic colorectal cancer patients: Straightforward or overcrowded?
abstract: Although the number of therapeutic options targeting tumour angiogenesis is becoming increasingly relevant, the question of the optimal choice for second-line anti-angiogenic inhibition in combination with chemotherapy for metastatic colorectal cancer patients remains largely unanswered. In fact the lack of head to head comparison between consolidated options such as bevacizumab and new treatment alternatives such as aflibercept and ramucirumab makes the selection in the clinical practice challenging, particularly when the patient has already received an anti-angiogenic-based combination up-front. In the following pages we described the biological scenario validating second-line angiogenesis inhibition in colorectal cancer along with potential mechanism of resistance. We also critically described the available evidence recommending the use of the bevacizumab, aflibercept and ramucirumab in this setting with the final aim to guide the choice in the clinical practice.
authors.affiliation: Medical Oncology Unit, Università Politecnica delle Marche, AOU "Ospedali Riuniti", Ancona, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.affiliation: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Caporale
authors.affiliation: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Braud
authors.affiliation: Medical Oncology, University Hospital of Parma, Parma, Italy.
authors.forename: Francesca V
authors.initials: FV
authors.lastname: Negri
authors.affiliation: Medical Oncology, National Cancer Institute "G. Paolo II", Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giuliani
authors.affiliation: Medical Oncology,University Hospital, University of Cagliari, Cagliari, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pusceddu
authors.affiliation: Medical Oncology,University Hospital, University of Cagliari, Cagliari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Demurtas
authors.affiliation: Colorectal Cancer Surgery, University Hospital, University of Cagliari, Cagliari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Restivo
authors.affiliation: Medical Oncology, University Hospital, Udine, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fontanella
authors.affiliation: Medical Oncology, University Hospital, Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Medical Oncology Unit, Università Politecnica delle Marche, AOU "Ospedali Riuniti", Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Medical Oncology,University Hospital, University of Cagliari, Cagliari, Italy. Electronic address: marioscartozzi@gmail.com.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D000096662:Ramucirumab
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins; D000096662:Ramucirumab; C533178:aflibercept
keywords: Aflibercept; Angiogenesis; Bevacizumab; Colorectal cancer; Ramucirumab; Second line