Bevacizumab (trade name Avastin/Avastin) is a recombinant humanized monoclonal antibody and an angiogenesis inhibitor that is used in the treatment of many cancers.
Bevacizumab has been approved in the United States and Europe for metastatic colorectal cancer, non-small cell lung cancer , metastatic renal cell carcinoma, and glioblastoma multiforme.
The primary mechanism of action of bevacizumab is to inhibit tumor microangiogenesis and arrest tumor progression by binding to human vascular endothelial growth factor A. It is a simple mechanism, but it can be used to inhibit tumor progression. A seemingly simple mechanism that can be used in the treatment of many cancers.
So how well does bevacizumab work when applied to liver cancer?
Effectiveness of bevacizumab for unresectable hepatocellular carcinoma
In 2008, the Journal of Clinical Oncology published a phase II clinical trial study of bevacizumab for unresectable hepatocellular carcinoma.
The study enrolled 46 patients with unresectable liver cancer and found that 65% of patients did not progress within 6 months of treatment, 50% did not progress within 6.9 months of treatment, and 53% survived longer than a year, with survival rates stabilizing over time.
Few of the patients had grade 3 to 4 adverse reactions. It is clear that bevacizumab has shown a good survival benefit and safety profile in patients with unresectable hepatocellular carcinoma.
New advances in bevacizumab for second-line treatment of advanced hepatocellular carcinoma
In 2016, the Anderson Cancer Center announced the results of another phase II clinical trial.
The study enrolled 44 patients with advanced hepatocellular carcinoma who were not candidates for surgery and local therapy and had failed sorafenib to be treated with bevacizumab in combination with erlotinib as a second-line regimen, and looked at its effectiveness and tolerability.
After 33.8 months of follow-up, 43% of patients had no tumor progression within 16 weeks of treatment, 50% of patients had no tumor progression within 3.9 months of treatment, and half of patients lived past 9.9 months, with rates of grade 3 to 4 adverse events ranging from 7% to 13%.
This shows that bevacizumab in combination with erlotinib is tolerable as a second-line treatment option for advanced hepatocellular carcinoma, and patients who received it showed a better survival benefit.
Of course, a subsequent phase III randomized controlled trial with more stringent screening criteria and a larger number of cases is needed to further validate its efficacy and safety.
Phase III trial of bevacizumab for hepatocellular carcinoma is underway
We know that whether a new drug is approved for registration and marketing depends on the results of the phase III clinical trial.
The lack of evidence from phase III trials has delayed the inclusion of bevacizumab in the “hepatocellular carcinoma” indication, which has greatly limited the use of bevacizumab in patients with hepatocellular carcinoma. This is especially true for patients who have failed surgery and other first-line therapies, or who are inoperable.
Just in March 2018, a study comparing the efficacy and safety of the “bevacizumab + atezumab (PD-1/PD-L1 inhibitor)” regimen with the “sorafenib (the only targeted drug approved for liver cancer today)” regimen The IMbrave 150 clinical trial was launched.
This study is the first open, randomized, controlled, phase III clinical trial to date to explore the effects of bevacizumab in liver cancer. The trial is still in “patient enrollment” status, but it is certainly promising for future expansion of bevacizumab in liver cancer.
Summary
Summary
Bevacizumab has demonstrated outstanding efficacy and safety in the exploration of first- and second-line therapy in patients with advanced hepatocellular carcinoma, especially in those who are not candidates for surgery and have failed other first-line therapies, offering a ray of hope for patients with advanced hepatocellular carcinoma.
Notably, the efficacy and safety of bevacizumab-containing first-line regimens in Asian populations has also been demonstrated in previous phase II clinical trials. This is an exciting result for patients with advanced liver cancer in Asia, including China.
While many of the relevant past studies have been multicenter, the number of patients included is still insufficient. Large-scale phase III randomized controlled clinical trials are still needed to further validate and explore different regimens and populations.