# The discovery of Bevacizumab. An historical reappraisal

## TL;DR

This paper reviews the history and clinical impact of Bevacizumab, a drug initially developed for cancer but later used for ocular diseases.

## Contribution

The paper provides a historical reappraisal of Bevacizumab's development and its variable clinical outcomes across different cancers.

## Key findings

- Bevacizumab was approved in 2004 for metastatic colorectal cancer but failed to improve survival in many other cancers.
- Biosimilars of Bevacizumab were approved in 2020 for cancer treatment.
- The drug's limitations include drug resistance and reduced chemotherapy delivery due to changes in tumor vasculature.

## Abstract

In 1997, the monoclonal antibody A4.6.1 was humanized to create Bevacizumab (Avastin, Genentech), an antibody suitable for clinical trials. In February 2004, Bevacizumab was approved in a randomized double-blind phase III study in which was administered in combination with bolus IFL (irinotecan, 5FU, leucovorin) chemotherapy as first-line therapy for previous untreated metastatic colorectal cancer. In 2020, the EMA approved the first biosimilar of Bevacizumab for the treatment of multiple types of cancer. The administration of Bevacizumab became popular among ophthalmologists for different ocular diseases. However, in most cases of cancers, including breast, melanoma, pancreatic and prostate cancer, Bevacizumab failed to increase survival. Despite impressive performances in animal models, however, inhibitors are not performing nearly as well in humans. The limitations of applying Bevacizumab are attributed to drug resistance, metastasis promotion and reduced delivery of chemotherapeutic agents, resulting from the dramatic decrease in tumor vasculature.