Trastuzumab Treatment in Multiple Lines: Current Data and Future Directions

Trastuzumab improves response rate, time to progression, and overall survival when combined with first-line chemotherapy in patients with human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer (MBC). However, the benefits of continuing trastuzumab beyond disease progression have not been clearly established. The literature was reviewed to obtain data on trastuzumab use beyond disease progression. In general, data from retrospective and observational studies suggest that there may be clinical benefit when trastuzumab is used beyond disease progression. These results are supported by prospective non-randomized studies. Response rates and survival outcomes have generally been superior in patients who have continued trastuzumab after disease progression compared with those who have not. Moreover, recent data from two prospective randomized phase III trials have shown that adding trastuzumab to the treatment regimen in patients with MBC who have progressed on trastuzumab-based therapy significantly prolongs progression-free survival. Emerging evidence from randomized controlled trials supports the potential clinical utility of continuing trastuzumab-based therapy beyond progression and supports the National Comprehensive Cancer Network recommendation to consider this treatment approach. Future treatment of HER2-positive MBC may involve trastuzumab being used in successive regimens in combination with other targeted therapies.