T-DM1 has demonstrated impressive efficacy with lower toxicity in a number of clinical trials for patients with HER2-positive metastatic breast cancer, resulting in the agent quickly becoming a standard of care in the refractory setting. Clinical trials continue to explore the treatment both as a single agent and in combinations.

The phase III MARIANNE trial examined T-DM1 plus or minus pertuzumab compared with trastuzumab plus a taxane for untreated patients with HER2-positive metastatic breast cancer. The primary endpoint of the study was progression-free survival, with secondary outcome mesures focused on adverse events, moderator Adam Brufsky, MD, PhD, notes.

In phase II studies, the frontline administration of T-DM1 demonstrated superior efficacy to trastuzumab and docetaxel. It seems likely this data will be replicated in the phase III setting, believes Hope S. Rugo, MD. Until results from the MARIANNE study are reported, it remains unclear whether the addition of pertuzumab will add to T-DM1's efficacy, suggests Rugo.

The MARIANNE study was designed prior to the reporting of data from the CLEOPATRA trial, which led to the approval of pertuzumab. As a result of this timing, the MARIANNE trial does not contain a trastuzumab, taxane, and pertuzumab arm. In CLEOPATRA, treatment with trastuzumab, docetaxel, and pertuzumab demonstrated an impressive 15.7-month improvement in overall survival compared with trastuzumab and docetaxel in women with HER2-positive breast cancer.