Metastatic Breast Cancer Treatment Challenges - Episode 5
For High-Definition, Click
In February 2013, the FDA approved T-DM1 (ado-trastuzumab emtansine; Kadcyla) for the treatment of patients with HER2-positive metastatic breast cancer. T-DM1 was the first antibody drug conjugate (ADC) to show activity in breast cancer, explains Edith A. Perez, MD. Furthermore, this novel drug design allows for the delivery of a potent chemotherapy agent directly to HER2-positive cells, effectively combining the efficacy of both agents while minimizing toxicity.
The approval of T-DM1 was based on data from the phase III EMILIA trial that compared the agent to lapatinib plus capecitabine, Perez continues. This trial globally enrolled 991 patients with advanced breast cancer, although only 978 received treatment. All accrued patients had been previously treated with trastuzumab and a taxane.
The trial had coprimary endpoints of progression-free survival (PFS) and overall survival (OS). T-DM1 demonstrated superiority over the doublet by significantly extending PFS by 3.2 months and OS by 5.8 months. Moreover, treatment with T-DM1 was associated with fewer side effects. These findings effectively shifted the global standard of care for these patients, Perez states.
Moderator, Adam M. Brufsky, MD, PhD, believes that several questions accompany the EMILIA trial, particularly since it is the first ADC to be approved in breast cancer. One of the lead questions, Brufsky suggests, involves future combinations and sequences for the agent. Furthermore, Brufsky believes, it remains unclear whether T-DM1 acts as a chemotherapy or an antibody. To address this, Andrew D. Seidman, MD, explains that, by itself, emtansine is very active but extremely toxic. Conjugating emtansine to trastuzumab preserves this efficacy and controls toxicity. However, treatment with T-DM1 seems to affect cells similarly to chemotherapy, Seidman believes.
The lingering question facing many breast oncologists is where to utilize this agent in the sequence. To help answer this question, the phase III MARIANNE trial is currently examining T-DM1 in combination with pertuzumab as a frontline treatment for patients with metastatic breast cancer.