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

Abstract

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 tumorinduced 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.

SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia

“…For cancer, this pathway has been extensively targeted for anti-angiogenesis. A monoclonal antibody targeting VEGF-A (bevacizumab, Avastin®) has been used as a cancer treatment [20]. A phase 1a clinical trial of NRP-1 antibody MNRP1685A (Vesencumab®), targeting the against VEGF-binding site of NRP-1, was well-tolerated in cancer patients [62], but neuropathy was noted.…”

Rapid Improvement of the Performance Status and Reduction of the Tumor Size in KRAS-Mutated Colorectal Cancer Patient Receiving Binimetinib, Hydroxychloroquine, and Bevacizumab

“…In particular, single-agent MEK inhibitors occasionally demonstrated tumor responses in patients with various RAS/RAF-mutated cancers [2,3], so it is not self-explanatory whether the same effect could be achieved with binimetinib alone, or, alternatively, the addition of hydroxychloroquine was critical for the improvement of the health status in this otherwise incurable patient. Bevacizumab was added to binimetinib plus hydroxychloroquine combination purely due to empirical assumptions, given that this drug improves the delivery of various therapies to tumor lumps and based on the extensive experience of using bevacizumab in CRC patients [8]. The patient is currently on observation, therefore, the degree of the maximal response and the duration of the disease control remain to be seen.…”

Repurposing anticancer drugs for the management of COVID-19

“…Bevacizumab is a monoclonal antibody with antiangiogenic properties, capable to target the vascular endothelial growth factor (VEGF) ( Garcia et al 2020 ). This biological agent has been successfully implemented in the clinic management of various cancer types, including advanced ovarian cancer, renal cell carcinoma, as well as colorectal cancer in combination with chemotherapy ( Garcia et al 2020 ; El Bairi et al 2017 ). The key mechanism of bevacizumab is related to the disruption of the malignant neo-angiogenesis, ultimately reducing the abnormal vascular permeability and nutrients supply to cancer cells.…”