Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars

Abstract

Colorectal cancer (CRC) is a leading cause of tumor-related morbidity and mortality worldwide, with mortality most often attributable to metastatic disease. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, has a significant role in the treatment of metastatic CRC (mCRC). However, patient access to bevacizumab may be limited in some regions or circumstances, owing to factors related to insurance coverage, reimbursement, patient out-of-pocket costs, or availability. As a result, outcomes for patients with mCRC may be worsened. Additionally, counterfeit bevacizumab has infiltrated legitimate supply chains, exposing patients to risk. Oncologists may also be affected detrimentally, since resolving access issues can be time-consuming and demoralizing. The imminent expiry of patents protecting bevacizumab provides other manufacturers with the opportunity to produce highly similar versions known as biosimilars. High-quality, safe, and effective biosimilars have the potential to expand access to bevacizumab. Most of the bevacizumab biosimilars currently in development are in clinical trials in patients with non-small-cell lung cancer, and future authorization for mCRC indications will, therefore, be based on extrapolation. This article reviews the current role of bevacizumab in the management of mCRC, the possible barriers associated with diminished access to bevacizumab, and the potential bevacizumab biosimilars in development. How biosimilars may impact the treatment of mCRC is also discussed.

Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer

“…Bevacizumab (Avastin; Genentech, Inc, South San Francisco, California) is a humanized immunoglobulin G (IgG) monoclonal antibody (mAb) directed against VEGF‐A, as depicted in Figure . Its potential mechanisms of action are believed to include the depletion of tumor vasculature as well as the temporary normalization of the crazy‐quilt pattern of tumor vasculature to enhance chemotherapy delivery . Bevacizumab also appears to be a mediator of antigen presentation …”

Screening of molecular targets and construction of a ceRNA network for oxaliplatin resistance in colorectal cancer

“…2 Although a variety of small molecule targeted drugs are widely used in clinical practice, oxaliplatin, a third-generation platinum drug, has not yet been challenged as the rst-line therapy for CRC. 3,4 Oxaliplatin is as an alkylating agent with the molecular formula 1,2-diaminocyclohexane (DACH), and can form DACH-DNA adducts and produce inter-or intra-chain crosslinks. This prevents the separation of DNA strands during transcription and translation, inducing cancer cell apoptosis.…”

Bevacizumab Biosimilars: Scientific Justification for Extrapolation of Indications

“…For instance, the potential biosimilar bevacizumab PF-06439535 was compared with bevacizumab-EU in combination with paclitaxel and carboplatin, a treatment regimen for which safety and efficacy profile in patients with advanced nonsquamous NSCLC is well understood [77]. Based on the treatment effect, using ORR as end point in clinical studies of originator bevacizumab [78], the NSCLC patient population was considered suitably sensitive to detect differences between the products should they exist [79]. In this double-blind, randomized, parallel-group clinical trial (NCT02364999), equivalence in the primary end point was demonstrated by week 19 [80], based on the 90% future science group www.futuremedicine.com CI of the relative risk of ORR of PF-06439535 versus bevacizumab-EU, which was within a prespecified margin of 76-132% [77].…”