Table 1.
Kinase inhibitors for the treatment of breast cancer
| Kinase inhibitor | Drug target | FDA approval status* |
|---|---|---|
| Lapatinib (Tykerb) | EGFR, HER2 | Initially approved in 2007 and currently indicated for (1) use in combination with capecitabine for the treatment of patients with advanced or metastatic HER2+ breast cancer and who have received prior therapy including an anthracycline, a taxane, and trastuzumab or (2) in combination with letrozole for the treatment of postmenopausal women with ER+HER2+ for whom hormonal therapy is indicated |
| Neratinib (Nerlynx) | EGFR, HER2, HER4 | Approved in 2017 for extended adjuvant treatment of early stage HER2+ breast cancer following adjuvant trastuzumab-based therapy and granted Orphan Drug Designation in 2019 for the treatment of breast cancer patients with brain metastases |
| Pyrotinib | EGFR, HER2, HER4 | Approved for clinical use in China in combination with capecitabine for the treatment of advanced or metastatic HER2+ breast cancer. Currently in Phase III clinical trials in the U.S. (NCT03980054, NCT03080805, NCT03863223, NCT02973737, NCT03588091) |
| Palbociclib (Ibrance) | CDK4, CDK6 | Granted accelerated approval in 2015 and currently indicated for the treatment of ER-HER2+ metastatic breast cancer in combination with (1) an aromatase inhibitor as initial endocrine-based therapy or (2) fulvestrant in patients who progressed on previous endocrine therapy |
| Ribociclib (Kisqali) | CDK4, CDK6 | Approved in 2017 and currently indicated for the treatment of ER-HER2+ metastatic breast cancer in combination with (1) an aromatase inhibitor as initial endocrine-based therapy or (2) fulvestrant as initial endocrine-based therapy or following progression on endocrine therapy |
| Abemaciclib (Verzenio) | CDK4, CDK6 | Granted priority review in 2015 and regular approval in 2017. Currently indicated for the treatment of ER+HER2- metastatic breast cancer in combination with (1) an aromatase inhibitor as initial endocrine-based therapy or (2) fulvestrant following progression on endocrine therapy or (3) as monotherapy in patients exhibiting disease progression following endocrine therapy and prior chemotherpy in the metastatic setting |
| Alpelisib (Piqray) | PI3K | Approved in 2019 for use in combination with fulvestrant for the treatment of HR+HER2- PIK3CA mutated advanced or metastatic breast cancer following progression on endocrine therapy |
| Everolimus (Afinitor) | mTOR | First approved in 2009 for the treatment of renal cell carcinoma and expanded to include treatment of ER+HER2- metastatic breast cancer in combination with exemestane following progression on letrozole or anastrozole |
*FDA approval statuses were found on the FDA website. Pyrotinib data referenced in[31]