Apatinib, a small molecule targeted anti-cancer drug developed in China, was approved for marketing by the Chinese State Food and Drug Administration (CFDA) on December 13, 2014, for the treatment of patients with advanced gastric adenocarcinoma or adenocarcinoma of the gastro-esophageal junction that has progressed after at least 2 lines of treatment.
While there is no indication for apatinib in the treatment of breast cancer, there are many studies of interest, including exploration in advanced breast cancer such as drug-resistant metastatic triple-negative breast cancer and metastatic non-triple-negative breast cancer.
Why does it work against cancer?
Like normal cells, tumor cells need blood to provide nutrients for growth, mainly from the large number of abnormal blood vessels surrounding the cancerous tissue. Vascular endothelial growth factor (VEGF) plays an important role in the process of angiogenesis. Tumor tissue usually secretes large amounts of VEGF, which binds to the vascular endothelial growth factor receptor (VEGFR) and promotes the frantic growth of blood vessels around the tumor.
Apatinib is a drug that selectively inhibits VEGFR-2, blocking downstream signaling and thus inhibiting the formation of neovascularization within tumor tissue. By cutting off the nutrient supply to the tumor, it theoretically inhibits tumor growth.
Metastatic triple-negative breast cancer: progression after treatment, still benefit 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 next 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. ; months. 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.
It is clear that in previously treated refractory metastatic triple-negative breast cancer, apatinib monotherapy can still provide some disease remission, but it is also important to be alert to its adverse effects, which are tolerated by most patients.
Metastatic non-triple-negative breast cancer: progression control with apatinib monotherapy remains up to 4 months after treatment failure
Studies have shown that apatinib has shown some efficacy in non-triple-negative breast cancer. The “non-triple negative” is hormone receptor-positive or HER2-positive breast cancer with a molecular typing that is not triple negative.
In a phase II clinical study, 38 patients with metastatic breast cancer were selected for study, most of whom had received several prior chemotherapies and had failed at least 1 endocrine therapy or targeted therapy.
These patients were treated with apatinib monotherapy, and the patients had a median progression-free survival of 4 months and a survival of more than 10 months. Thirty-six of these patients had a remission rate of 16.7% and a disease control rate of 66.7% after treatment.
The most common moderate adverse reactions to apatinib treatment included hypertension (20.5%), hand-foot syndrome (10.3%), and proteinuria (5.1%), with three patients experiencing serious adverse reactions.
Advanced breast cancer: multi-drug resistance is still an option with apatinib
For multidrug-resistant advanced breast cancer, one study analyzed apatinib treatment in 24 patients, with a remission rate of more than 40%, a disease control rate of 83.3%, and tumor progression in only 4.
Progression-free survival in patients treated with apatinib was 4.7 months, and overall survival was 8.0 months. Major adverse reactions during dosing included proteinuria, hypertension, fatigue, skin reactions in the hands and feet, and hyperbilirubinemia.
It is clear that even in advanced breast cancer that is multi-drug resistant, apatinib monotherapy has shown efficacy and may be an option after other treatments have failed.
What is the status of apatinib in the study?
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;
- Application in different treatments, such as for neoadjuvant chemotherapy;
- Studies of efficacy prediction.
Summary
Advanced breast cancer, whether triple-negative, hormone receptor-positive, or HER2-positive, can still achieve some tumor control with apatinib after failure of multiple drug therapies.
Apatinib has an outstanding anti-vascular therapy effect, and we look forward to more breakthroughs in breast cancer research in the future to benefit more patients.