Ado-trastuzumab emtansine (T-DM1) improved survival in women with HER2-positive breast cancer, even after treatment with two or more other HER2-targeted therapies, including trastuzumab and lapatinib, according to results of a phase III randomized trial, TH3RESA, presented at the 2015 San Antonio Breast Cancer Symposium (abstract S5-05).
“T-DM1 demonstrated a clinically meaningful and statistically significant improvement in overall survival compared to a treatment of physician’s choice,” said study author and presenter Hans Wildiers, MD, PhD, a professor of medical oncology at KU Leuven in Belgium, at a press conference.
Median overall survival improved by 6.9 months from 15.8 months in the control arm to 22.7 months in the T-DM1–treated arm after a median follow-up of 30.5 months (hazard ratio [HR], 0.68; P = .0007).
Positive efficacy, including improved progression-free survival, and safety data from TH3RESA were previously presented at the 2013 European Cancer Congress.
T-DM1 is a HER2-targeted antibody–drug conjugate that links trastuzumab with a cytotoxic agent. The drug was approved by the US Food and Drug Administration in 2013 as a monotherapy for HER2-positive, metastatic breast cancer that had progressed after treatment with trastuzumab and a taxane, either separately or in combination.
While breast cancer guidelines now recommend T-DM1 in patients previously treated with trastuzumab, many patients received other second- or later-line therapies before these guidelines were put in place. The current trial, according to Dr. Wildiers, tested whether these later-line patients would benefit from T-DM1.
The international trial randomized 602 patients 2:1 to either 3.6 mg/kg intravenous T-DM1 every 3 weeks or treatment of physician’s choice—either HER2-directed regimens (83.2%) or single-agent chemotherapy (16.8%).
Patients had a survival benefit from T-DM1 regardless of age, hormone-receptor status, visceral metastases, and number of prior treatment regimens.
Grade 3 or higher adverse events occurred more frequently in patients in the control arm compared with those in the T-DM1 arm (47.3% and 40%, respectively). Grade 3 or higher adverse events that occurred in at least 3% of patients included neutropenia (2.5% with T-DM1 vs 15.8% in the control arm), febrile neutropenia (0.2% with T-DM1 vs 3.8%), and diarrhea (0.7% with T-DM1 vs 4.3%). Grade 3 thrombocytopenia occurred more frequently with T-DM1 (6% vs 2.7%).
At the cutoff date of February 2015, one quarter of patients had not yet progressed, said Wildiers.
“We used to think that HER2 was the most aggressive form of [breast cancer] … and now with our treatments that directly target HER2, it has actually turned out to be a better tumor to have,” said moderator of the conference, Kent Osborne, MD, co-director of the San Antonio Breast Cancer Symposium and director of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. “This is just another example of that.”
The study was supported by Roche, the manufacturer of T-DM1.