Table 2.
Drugs developed to target Herceptin-resistant Her2+ breast cancer.
| Anti-Her2 drug | Mechanism of Action | Status |
|---|---|---|
| Lapatinib | small molecule tyrosine kinase inhibitor of EGFR1/Her1/Her2 that binds to intracellular domain of Her1 & Her2 | Approved in combination with endocrine therapy and capecitabine for the treatment of hormone receptor-positive Her2+ metastatic breast cancer in patients who have progressed on chemotherapy and Herceptin |
| Pertuzamab | monoclonal antibody that targets an epitope of the extracellular domain of Her2 | Approved for use in metastatic Her2+ breast cancer in combination with docetaxel as first-line therapy |
| TDM-12 | antibody-drug conjugate linking Herceptin to emtansine | Results of Phase III studies in patients with pre-treated locally advanced and metastatic Her2+ breast cancer recently reported |
| Neratinib | low-molecular weight, irreversible tyrosine kinase inhibitor with activity against Her1, Her2 & Her4 | Several Phase III trials of Neratinib combination therapy in adjuvant and metastatic setting underway (ExteNET3, NEFERRT4) |
| mTOR inhibitors | targets against the PI3K/AKT/mTOR5 pathway in Her2+ breast cancer | Phase III trials of Everolimus with Herceptin and Paclitaxel (BOLERO-16) or vinorelbine (BOLERO-37) in pretreated locally advanced or metastatic Her2+ breast cancer underway |
| Bevucizamab | monoclonal antibody that targets VEGF8, inhibits angiogenesis and delays tumor growth | BETH trial (Bevucizamab + Herceptin + chemo) in adjuvant setting in node-positive or high-risk node-negative Her2+ breast cancer has completed accrual; report of results pending |
Epidermal growth factor;
Trastuzamab emtansine;
Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer;
Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab Plus Paclitaxel In ErbB-2 Positive Advanced Breast Cancer;
Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin;
A randomized, phase III, double-blind, placebo-controlled multicenter trial of everolimus in combination with trastuzumab and paclitaxel as first-line therapy in women with HER2-positive, locally advanced or metastatic breast cancer;
Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer;
Vascular endothelial growth factor