Hans Wildiers, MD, PhD
Although T-DM1 (ado-trastuzumab emtansine; Kadcyla) is already approved by the FDA as a treatment for patients with HER2-positive breast cancer previously treated with trastuzumab (Herceptin) and a taxane, findings from the TH3RESA study1
also support the regimen as a standard of care for heavily pretreated patients, explains Hans Wildiers, MD.
, Wildiers, lead author on the TH3RESA study and a professor of Medical Oncology at KU Leuven in Belgium, provides an overview of TH3RESA and discusses the trial’s significance in the field of HER2-positive breast cancer.
OncLive: What was the design of the phase III TH3RESA study?
: The TH3RESA study is a randomized study comparing T-DM1 versus a treatment of physician’s choice in patients with HER2-positive metastatic breast cancer. T-DM1 is an antibody-drug conjugate composed of trastuzumab, stably linked to a DM1 cytotoxic microtubule inhibitor. T-DM1 is already approved in HER2-positive metastatic breast cancer.
After a median follow-up of 30 months, OS improved by 6.9 months. It went from 15.8 months for patients in the control arm to 22.7 months for those in the T-DM1 arm, which was highly significant. Because of that effect, at least 50% of patients in the control arm crossed over to T-DM1 at progression.
What are the clinical implications of these findings?
The TH3RESA study confirms the EMILIA study. Both trials show that, if you use T-DM1 in patients with HER2-positive metastatic breast cancer who received a taxane and trastuzumab, T-DM1 is the preferred regimen in that setting.
This is also why the NCCN guidelines exactly state that T-DM1 is the preferred regimen in this setting.
Were there any concerning toxicities with T-DM1?
T-DM1 has a favorable safety profile. There was slightly more thrombocytopenia in the T-DM1 arm. However, other toxicities, such as febrile neutropenia, diarrhea, and nausea, were all clearly higher in the control arm.
Importantly, we achieved a nearly 7-month overall survival benefit with less toxicity.
Wildiers H, Kim S-B, Gonzalez-Martin A, et al. Trastuzumab emtansine improves overall survival versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer: Final overall survival results from the phase 3 TH3RESA study. Presented at: 2015 San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. Abstract S5-05.
Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783-1791.
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