• 991 patients: PFS and OS favored T-DM1 versus capecitabine and lapatinib (PFS: 9.6 mo versus 6.4 mo; OS: 30.9 mo versus 25.1 mo).
• T-DM1 was well tolerated, but transient thrombocytopenia and minor LFT abnormalities were observed.

Perhaps the most important new oncologic agent in the past decade, T-DM1 will instantly transform the way clinicians approach the management of HER2-positive metastatic disease, once it is approved, based on findings from this seminal "second-line" study. However, massive upheaval of traditional treatment algorithms could really be in store, hopefully soon, when we receive data from the already accrued MARIANNE trial comparing this novel antibody-drug conjugate, alone or in combination with pertuzumab, to trastuzumab with a taxane in the front-line setting. Beyond providing important clues about the efficacy of this agent, the results of that study have the potential to offer patients something quite special — an effective treatment that comes without many of the toxicities commonly associated with chemotherapy.