Chicago, IL—The novel antibody drug conjugate trastuzumab emtansine (T-DM1) significantly extended progression-free survival (PFS) and was very well tolerated in the first results of the international EMILIA trial, which were presented at the 2012 American Society of Clinical Oncology (ASCO) meeting.
“The drug worked. It was significantly better than a very effective approved therapy for HER2-overexpressing metastatic breast cancer,” said Kimberly L. Blackwell, MD, Associate Professor of Medicine in the Division of Hematology-Oncology at Duke Cancer Institute at Duke University, Winston-Salem, NC, at the ASCO plenary session.
EMILIA randomized 991 HER2-positive patients with advanced breast cancer who were previously treated with a taxane and trastuzumab. Patients received T-DM1 or capecitabine plus lapatinib (XL) every 3 weeks until progression.
At a median follow-up time of approximately 12 months, patients receiving T-DM1 had a median PFS of 9.6 months compared with 6.4 months for XL, which was a 35% highly significant reduction in risk (P <.001), Dr Blackwell reported.
The efficacy was consistent across all prespecified patient subgroups, and only in women aged ≥65 years was T-DM1 not superior to established treatment.
Median overall survival (OS) was not reached with T-DM1 compared with 23.3 months median OS with XL. This amounted to a 38% reduction in mortality risk (P = .005), although it did not meet the prespecified threshold for significance at the first analysis.
Despite the lack of significant OS difference as prespecified, after 2 years in the trial, 65.4% of the patients receiving T-DM1 were alive compared with 47.5% of those receiving XL, Dr Blackwell noted, adding, “There is an apparent survival benefit with T-DM1.”
Louis M. Weiner, MD, Director of the Georgetown-Lombardi Cancer Center in Washington, DC, and the invited discussant of the presentation, agreed that a statistically significant OS benefit will eventually be observed with T-DM1. “This would be particularly notable, since effective palliative treatment has rarely been associated with improved survival in the meta-static setting,” he pointed out.
T-DM1 also has the advantage of being very well tolerated. Dose reductions were required only for 16.3% of patients receiving T-DM1 compared with 53.4% for capecitabine and 27.3% for lapatinib. The most common grade 3 or higher adverse events for T-DM1 were thrombocytopenia and transient elevations in liver function tests. As expected, patients receiving XL experienced significantly more diarrhea, hand-foot syndrome, and vomiting.
T-DM1 “Really Works”
“Stated simply, T-DM1 really works in this patient population,” Dr Weiner said. “It is an important new weapon in the therapeutic armamentarium for breast cancer.”
Future studies will need to validate the results and to elucidate the mechanisms of tumor control with this novel agent, he said. “But the very clean design and institution of this study, coupled with the compelling results, make it unlikely that additional studies will fail to confirm these important findings,” he suggested.
“Needless to say, T-DM1 merits evaluation for previously untreated HER2-overexpressing metastatic breast cancer and ultimately may find utility in adjuvant and neoadjuvant management, and perhaps in other HER2-overexpressing cancers,” Dr Weiner predicted. “Such trials are planned or are in progress.”
