Frontline treatment with T-DM1 (ado-trastuzumab emtansine; Kadcyla) is currently being explored for patients with HER2-positive metastatic breast cancer in several phase III trials. These large studies were preceded by successful phase II investigations, including the TDM4450g study.

In this study, T-DM1 was compared to trastuzumab plus docetaxel in 137 women with previously untreated, HER2-positive metastatic breast cancer. Overall, notes Sara Hurvitz, MD, T-DM1 was associated with an improvement in progression-free survival of approximately 5 months. Additionally, there was significantly less toxicity with T-DM1, including over a 50% reduction in grade 3/4 adverse events.

Additionally, the phase III MARIANNE trial is examining T-DM1 plus or minus pertuzumab compared to trastuzumab plus a taxane. This large global trial enrolled 1095 patients nearly a year earlier than expectations, Edith A. Perez, MD, explains. The last patient was enrolled to the trial in May 2012 and early results are expected by 2014, potentially at the ASCO Annual Meeting.

The MARIANNE trial is powered to allow for the comparison of both investigational arms to the control. Additionally, it will allow for a comparison directly between the two investigational arms. The results from this trial could potentially be practice changing, Perez believes.

One of the end results of this trial will be to learn whether T-DM1 with pertuzumab or T-DM1 alone is better than a taxane plus trastuzumab, remarks Andrew D. Seidman, MD. However, it will not provide data on whether these approaches are superior to a taxane plus trastuzumab and pertuzumab, which was explored in the CLEOPATRA trial.