San Antonio, Texas - Among patients with HER2-positive, metastatic breast cancer that had progressed despite treatment with two or more forms of HER2-targeted therapy (trastuzumab [Herceptin] and lapatinib [Tykerb]), median overall survival was increased for those treated with trastuzumab emtansine (T-DM1 [Kadcyla]) compared with those who received treatment of physician’s choice, according to results from the phase III TH3RESA clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held December 8–12.

The HER2-targeted antibody-drug conjugate T-DM1 was approved by the U.S. Food and Drug Administration in February 2013 for treating patients with HER2-positive, metastatic breast cancer that had progressed after treatment with trastuzumab and a taxane.

“The National Comprehensive Cancer Network guidelines, which are widely used as the standard for cancer care, were recently changed to recommend using T-DM1 as a preferred treatment for patients with trastuzumab-exposed HER2-positive, metastatic breast cancer, meaning that it is generally used after a patient’s metastatic disease has progressed following treatment with a combination of a taxane-based chemotherapy and trastuzumab, with or without pertuzumab (Perjeta),” said Hans Wildiers, MD, PhD, a professor of medical oncology at KU Leuven in Belgium. “However, there are a lot of patients who received second- or later-line treatment before this recommendation was put in place and TH3RESA was designed to establish whether T-DM1 could benefit patients in later lines as well.

“Previously published results from TH3RESA showed that T-DM1 almost doubled progression-free survival,” continued Wildiers. “Here we show that T-DM1 actually increased overall survival for heavily pretreated patients with HER2-positive, metastatic breast cancer. This is very important because several breast cancer therapies that increase progression-free survival do not in fact increase overall survival, and these patients urgently need new treatment options.”

All 602 patients with HER2-positive, metastatic breast cancer enrolled in TH3RESA had been previously treated with a chemotherapy regimen that included a taxane and, after a diagnosis of metastatic disease, two or more regimens that included HER2-targeted therapeutics, including trastuzumab and lapatinib. Patients were randomly assigned 3.6 milligrams of T-DM1 per kilogram of body weight every three weeks or treatment of physician’s choice.

After a median follow-up of 30.5 months, the median overall survival was significantly longer among the 404 patients assigned T-DM1 compared with the 198 patients assigned treatment of physician’s choice: 22.7 months compared with 15.8 months. The overall survival benefit was seen regardless of patient age, hormone-receptor status, visceral involvement, and number of prior treatment regimens.

The incidence of grade 3 or higher adverse events was higher among patients assigned treatment of physician’s choice compared with those assigned T-DM1: 47.3 percent compared with 40.0 percent.

“Not only did the population of patients assigned T-DM1 have increased median overall survival, they also had reduced incidence of grade 3 and higher adverse events,” said Wildiers. “The fact that these patients lived longer with less toxicity suggests that T-DM1 is a good treatment option even for patients who have received two or more HER2-targeted treatment regimens.”

This study was supported by Roche. Wildiers’ institution has received compensation from Roche for lectures he has presented at national meetings and for consulting work, as well as an unrestricted research grant for academic research.