title: [Anti-angiogenic treatments in metastatic colorectal cancer: Does a continuous angiogenic blockade make sense?].
abstract: Ten years after the approval of bevacizumab in colorectal cancer patients, results from ML18147 and CORRECT studies have recently demonstrated the possibility to target angiogenesis in patients previously exposed to anti-VEGF. An increasing number of anti-angiogenic treatments are now available, however, no biomarker has yet succeeded in rationalizing our therapeutic strategies. Nevertheless, several lessons have been learned from preclinical and pivotal clinical studies. The first clinical trials demonstrated a survival benefit, adding VEGFA targeting monoclonal antibodies to chemotherapy in metastatic colorectal cancer patients (AVF2107, ECOG 3200). Many phase III clinical trials confirmed the interest of this strategy, in combination with chemotherapies containing irinotecan, oxaliplatin, or with 5-fluorouracil in monotherapy. To date, such results have not been reproduced with tyrosine kinase inhibitors targeting the angiogenesis pathways, with an increasing rate of chemotherapy related toxicities. Clinical trials performed in the adjuvant setting (AVANT, NSABPC08) failed to demonstrate any efficacy of the anti-VEGFA treatments on the micrometastatic disease, encouraging its prescription in the unresectable cases. On the other hand, a continuous inhibition of angiogenesis during the course of the metastatic disease was shown to be feasible and to extend colon cancer patient's survival in two recent randomized trials. For these patients, the continuation of bevacizumab beyond progression in first line improves overall survival. Lastly, results achieved by the CORRECT and CONCUR studies demonstrated that anti-angiogenics might be effective in colorectal cancers resistant to chemotherapy. This review presents the main results of preclinical and clinical studies sustaining the prescription of anti-angiogenics in metastatic colorectal cancers. The future challenge is to promote the development of biomarkers to enable the stratification of the different therapeutic strategies.
authors.affiliation: CHRU de Besançon, IRFC, service d'oncologie médicale, 25000 Besançon, France. Electronic address: mjary@chu-besancon.fr.
authors.forename: Marine
authors.initials: M
authors.lastname: Jary
authors.affiliation: CHRU de Besançon, IRFC, service d'oncologie médicale, 25000 Besançon, France; Unité Inserm 1098, université de Franche-Comté, 25000 Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: CHU de Reims, services de gastroentérologie et d'oncologie médicale, 51100 Reims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: CHRU de Besançon, IRFC, service d'oncologie médicale, 25000 Besançon, France.
authors.forename: Stéfano
authors.initials: S
authors.lastname: Kim
authors.affiliation: Hôpital Saint-Antoine, service d'oncologie médicale, 75012 Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.affiliation: Institut de cancérologie de l'Ouest, Nantes-Angers, 44805 Nantes, France.
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D016032:Randomized Controlled Trials as Topic; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin
keywords: Aflibercept; Anti-angiogenic; Anti-angiogénique; Bevacizumab; Bévacizumab; Cancer colorectal; Colorectal cancer; Maintenance therapy; Regorafenib; Régorafénib; Traitement d’entretien