HER2-positive metastatic breast cancer: New agents on the horizon

The human epidermal growth factor receptor HER2/neu gene is amplified and overexpressed in 25 to 30% of breast cancers. In women with HER2-positive advanced or metastatic breast cancer, the anti-HER2 monoclonal antibody trastuzumab and the dual tyrosine kinase inhibitor lapatinib are both established options used in combination with cytotoxic chemotherapy. In patients who progress after first-line therapy with trastuzumab plus chemotherapy, continued trastuzumab or switching to lapatinib, both in combination with cytotoxic chemotherapy, offers clinical benefit. New agents in the metastatic disease setting include pertuzumab and trastuzumab emtansine. In the first-line setting, the addition of pertuzumab to trastuzumab/docetaxel yields longer median progression-free survival than placebo plus trastuzumab/docetaxel (18.5 vs. 12.4 months; p < 0.001). In the second-line setting, trastuzumab emtansine alone improves median progression-free survival compared with capecitabine plus lapatinib (9.6 vs. 6.4 months; p < 0.0001). The combination of trastuzumab emtansine plus pertuzumab has also shown encouraging preliminary activity. Other agents in clinical development include subcutaneous trastuzumab, afatinib, and neratinib. Numerous other treatments across a range of drug classes are currently in development for the treatment of HER2-positive metastatic breast cancer.