Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook.

When the VEGF-A-targeting monoclonal antibody bevacizumab (Avastin®) entered clinical practice more than 15 years ago, it was one of the first targeted therapies and the first approved angiogenesis inhibitor. Marking the beginning for a new line of anti-cancer treatments, bevacizumab remains the most extensively characterized anti-angiogenetic treatment. Initially approved for treatment of metastatic colorectal cancer in combination with chemotherapy, its indications now include metastatic breast cancer, non-small-cell lung cancer, glioblastoma, renal cell carcinoma, ovarian cancer and cervical cancer. This review provides an overview of the clinical experience and lessons learned since bevacizumab's initial approval, and highlights how this knowledge has led to the investigation of novel combination therapies. In the past 15 years, our understanding of VEGF's role in the tumor microenvironment has evolved. We now know that VEGF not only plays a major role in controlling blood vessel formation, but also modulates tumor-induced immunosuppression. These immunomodulatory properties of bevacizumab have opened up new perspectives for combination therapy approaches, which are being investigated in clinical trials. Specifically, the combination of bevacizumab with cancer immunotherapy has recently been approved in non-small-cell lung cancer and clinical benefit was also demonstrated for treatment of hepatocellular carcinoma. However, despite intense investigation, reliable and validated biomarkers that would enable a more personalized use of bevacizumab remain elusive. Overall, bevacizumab is expected to remain a key agent in cancer therapy, both due to its established efficacy in approved indications and its promise as a partner in novel targeted combination treatments.

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Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. Garcia is employee of F. Hoffmann-La Roche Ltd. Dr. Hurwitz reports grants and personal fees from F. Hoffmann-La Roche Ltd./Genentech, Inc., outside the submitted work; and is employee of Genentech, Inc. Dr. Sandler is employee of Genentech, Inc.; in addition, Dr. Sandler has a patent related to a Taxol, Carboplatin, Tecentriq® and Avastin® regimen. Dr. Miles reports honoraria from F. Hoffmann-La Roche Ltd./Genentech, Inc. and acted in a consulting/advisory role for F. Hoffmann-La Roche Ltd./Genentech, Inc. outside the submitted work. Dr. Coleman reports grants from the NIH, the Gateway Foundation and the V Foundation; and grants from AstraZeneca, Merck, Clovis, Genmab, F. Hoffmann-La Roche Ltd./Genentech, Inc. and Janssen; and personal fees from AstraZeneca, Tesaro, Medivation, Clovis, Gamamab, Genmab Roche/Genentech, Janssen, Agenus, Regeneron and OncoQuest outside the submitted work. Dr. Deurloo is employee of F. Hoffmann-La Roche Ltd. Dr. Chinot reports honoraria and non-financial research support from F. Hoffmann-La Roche Ltd., and acted in a consulting/advisory role for F. Hoffmann-La Roche Ltd., outside the submitted work; in addition, Dr. Chinot has a patent related to a plasmatic biomarker of bevacizumab efficacy (Europe 12305565.9) issued to the Aix-Marseille University.