Apatinib, a small-molecule targeted anticancer drug developed in China, was approved for marketing by the Chinese State Food and Drug Administration (CFDA) on 2014 12 13 for the treatment of patients with advanced gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction that has progressed after at least 2 lines of treatment.
While there is no indication for its use in breast cancer, several studies have confirmed the efficacy of apatinib in treating metastatic triple-negative breast cancer.
Why does apatinib work against cancer?
The large number of abnormal blood vessels present around the tumor provides nutrition for tumor growth. Vascular endothelial growth factor (VEGF) plays an important role in the process of angiogenesis, and tumors secrete large amounts of this factor to stimulate wild blood vessel proliferation in tumor tissue.
Apatinib is a selective inhibitor of vascular endothelial growth factor receptor 2, blocking stimulatory signaling and thus inhibiting neovascularization within the tumor tissue. By cutting off the nutritional supply to the tumor, it theoretically inhibits tumor growth.
Metastatic triple-negative breast cancer: progression after treatment, still benefits from apatinib monotherapy
Clinical trials of apatinib for breast cancer have focused on advanced triple-negative breast cancer, and several studies have demonstrated the efficacy of apatinib.
In a phase IIa study, 25 patients with breast cancer who had failed prior anthracycline- and/or paclitaxel-based chemotherapy, all without exception, were triple negative. These patients were treated with apatinib alone, with 8 achieving remission and 9 having stable disease. Of the patients who achieved disease remission, 2 had serious adverse effects.
In the subsequent phase IIb study, 56 patients with advanced triple-negative breast cancer were treated with apatinib, with an overall remission rate of only 10.7%, a clinical benefit rate of 25%, and progression-free survival and overall survival of 3.3 months and 10.6 months, respectively. However, there were 2 patients who were not treated well and maintained remission at the end of follow-up, with progression-free survival up to 14.7 months and 30 months, respectively.
In terms of dosing safety, approximately 30% of patients had their dose adjusted during apatinib treatment due to adverse events. Common hematologic toxicities include thrombocytopenia, leukopenia, neutropenia, and anemia, as well as skin reactions in the hands and feet, proteinuria, hypertension, and elevated transaminases. These adverse reactions are mostly mild to moderate and are largely tolerated by patients after treatment.
There was also a small study that retrospectively analyzed the treatment of 8 patients with advanced disease, and apatinib was able to control tumor progression.
Study of Apatinib
The use of apatinib in breast cancer is still being explored, including:
- Studies in different breast cancers, such as locally recurrent or metastatic breast cancer, HER2 -negative breast cancer, advanced triple-negative breast cancer, early triple-negative breast cancer;
- Studies in combination with different drugs, including combination with docetaxel, capecitabine, paclitaxel, vincristine, exemestane, etc;
- Use in different treatments, such as for neoadjuvant chemotherapy;
- More studies to predict efficacy.
Summary
For metastatic triple-negative breast cancer, apatinib monotherapy is a promising agent for achieving some tumor control even after failure of multiple drug therapy. Its application requires vigilance for adverse effects.
Given the antivascular profile of this drug, we expect more studies to be conducted in breast cancers with high vascular dependence, and for efficacy prediction studies to be answered soon, so that more breast cancer patients can benefit from it.