Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy regimens for HER2-positive early breast cancer

Trastuzumab-based adjuvant therapy has become the standard of care for human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (EBC). Both anthracycline- and non-anthracycline-containing trastuzumab regimens are approved in the United States, but cardiotoxicity is increased with anthracycline-containing regimens. This paper reviews published and reported efficacy and cardiac safety data from the adjuvant trastuzumab trials [National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31/North Central Cancer Treatment Group (NCCTG) N9831, Breast Cancer International Research Group (BCIRG) 006, Herceptin Adjuvant (HERA), FinHer, and Programme Adjuvant Cancer Sein (PACS) 04]. The addition of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (from 24% to 58%) in five of the six trials. Overall survival was significantly improved (23%–35%) in the large trials. In NSABP B-31/ NCCTG N9831, 5.0%–6.6% of patients who received doxorubicin and cyclophosphamide (AC) were unable to receive trastuzumab. Cardiac event rate was highest in the anthracycline-containing trastuzumab arms (1.9%–3.8%) and lowest with the regimen of docetaxel, carboplatin, and trastuzumab (TCH) (0.4%). Incorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens.