Anti-HER2 Therapy Beyond Second-Line for HER2- Positive Metastatic Breast Cancer: A Short Review and Recommendations for Several Clinical Scenarios from a Spanish Expert Panel

Background: The aim of this project was to provide an expert opinion regarding anti-human epidermal growth factor receptor 2 (HER2) therapy beyond second-line treatment of metastatic breast cancer (mBC). Methods: A group of experts discussed specific issues concerning anti-HER2 therapy in late-line settings in mBC. Results: Trastuzumab emtansine (T-DM1) or dual HER2 blockade appeared to be good options for HER2-positive mBC after ≥ 2 HER2-targeted therapies. Once an objective response has been achieved with anti-HER2-containing therapy, the anti-HER2 agent can be continued until progression of the disease, unacceptable toxicity or patient decision. mBC treated with ≥ 3 consecutive lines of anti-HER therapy, ≥ 1 being a dual HER2 blockade and with early progression of disease during a fourth or later-line treatment, are clinically resistant to anti-HER therapy. For progression of metastasis in the brain after anti-HER2 therapy, lapatinib and chemotherapy appear to be a good alternative after best local treatment. Conclusions: Further clinical trials are needed to provide valuable knowledge about the best treatment options in the later settings of mBC.