Remolumab (Ramucirumab) is a monoclonal antibody that works to fight tumor angiogenesis. The drug was approved for marketing by the U.S. Food and Drug Administration (FDA) in April 2014 for the treatment of patients with progressive gastric cancer or adenocarcinoma of the gastroesophageal junction.
Currently, ramolutumab has not been officially approved for the treatment of breast cancer and is not available in China, and its role in breast cancer treatment appears to be unclear. In the face of the intractable situation of advanced breast cancer, can ramolutumab be a battle?
How does anti-angiogenesis work to kill tumors?
The development of cancer is not only related to the malignant proliferation of the tumor cells themselves, but the surrounding “microenvironment” is also an important factor. The large number of abnormal blood vessels in the tumor tissue imbalances the normal “microenvironment” and accelerates tumor progression.
Vascular endothelial growth factor (VEGF) is a cytokine that is overproduced in breast cancer tissue and is one of the main causes of tumor angiogenesis.
Remolumab prevents VEGF in tumor cells from transmitting signals that promote angiogenesis, thereby inhibiting neovascularization, degrading existing abnormal blood vessels, and promoting a rebalanced tumor microenvironment that helps other drugs to better kill tumors. Therefore, ramulizumab is mostly used in combination with other drugs.
Combination with docetaxel or eribulin: efficacy to be proven
In a small study conducted in Japan, 7 patients with advanced disease were treated with ramolumab in combination with docetaxel, with 4 patients achieving some degree of remission. Patients responded well to ramolumab during treatment and were less likely to develop drug resistance. Most adverse reactions were mild to moderate and tolerated.
In another large clinical study, 1144 inoperable HER2-negative patients with advanced breast cancer were treated with docetaxel alone and ramolutumab in combination with docetaxel. The results showed that the addition of ramolumab did not result in an improvement in survival time for the patients. Moreover, the use of ramolutumab was accompanied by more adverse effects.
But in another study, ramolutumab delayed the progression of advanced breast cancer by 1.5 months.
In a phase II study of eribulin (Eribulin) in combination with ramolumab for locally recurrent or metastatic breast cancer, patient survival was also not significantly prolonged. These conflicting results remind us that the status and role of the antiangiogenic agent ramolumab in advanced breast cancer remains unclear.
Other research advances
A phase II study of ramolutumab in combination with capecitabine in unresectable locally advanced or metastatic breast cancer is now complete, but results have not yet been published.
Studies are ongoing to determine whether the combination of ramolumab with immunotherapy, in addition to combination chemotherapy, can provide a first-line treatment opportunity for hormone-receptor-positive advanced breast cancer.