Amsterdam, The Netherlands—The antibody-conjugate ado-trastuzumab emtansine (Kadcyla), also known as T-DM1, prolonged progression-free survival (PFS) in advanced HER2-positive breast cancer in a heavily pretreated population, according to the final results of the phase 3 clinical trial TH3RESA. The study included cancer that progressed with ≥2 previous HER2-directed therapies—trastuzumab (Herceptin) and lapatinib (Tykerb).
TH3RESA extends the results of the EMILIA trial, in which T-DM1 extended PFS versus capecitabine (Xeloda)/lapatinib in HER2-positive advanced breast cancer in women previously receiving trastuzumab and a taxane. T-DM1 was granted US Food and Drug Administration approval for patients with previously treated progressive metastatic HER2-positive breast cancer based on the results from EMILIA.
“In TH3RESA, T-DM1 achieved a significant improvement in PFS, and the effect was clear and consistent across subgroups. These data affirm the results of EMILIA, demonstrating a consistent PFS benefit of T-DM1 in patients with previously treated HER2-positive advanced breast cancer,” said Hans Wildiers, MD, PhD, Department of Medical Oncology/Multidisciplinary Breast Centre, University Hospitals Leuven, Belgium. Dr Wildiers presented these results at the 2013 European Cancer Congress.
“T-DM1 should become the new standard of care for second-line treatment,” he stated.
Positive Data from TH3RESA
TH3RESA enrolled 602 patients with advanced breast cancer who were previously treated with at least 2 HER2-directed therapies, and randomized them in a 2:1 ratio to T-DM1 or to physician’s choice of chemotherapy (83% received trastuzumab-based regimens and 17% received chemotherapy). Treatment was continued until disease progression. Patients were allowed to cross over to T-DM1 at progression.
The median PFS was 6.2 months for T-DM1 versus 3.3 months in the control arm, representing almost a doubling of PFS. The PFS difference between groups was significant (P <.001).
A prespecified subgroup analysis showed similar PFS results favoring T-DM1 across all subgroups, including age, geographic area, race, performance status, tumor characteristics, and visceral disease.
Dr Wildiers also presented the first interim analysis of overall survival (OS) from TH3RESA—the median OS was 40.9 months in the control arm and was “not yet reached” for T-DM1. Longer-term follow-up will determine if there is a survival advantage with this drug.
No new safety signals for T-DM1 were reported in TH3RESA. Adverse events of grade ≥3 were more frequent in the control arm—43.5% versus 32.3% in the T-DM1 arm. Adverse events leading to discontinuation of therapy occurred in 10.9% of controls versus 6.7% of the T-DM1 group. The rate of cardiac events was low in both arms—left-ventricular ejection fraction <50 was reported in 1.1% and 1.5% of the patients, respectively.
First-line therapy with T-DM1 is being evaluated in an ongoing phase 3 clinical trial in advanced HER2-positive breast cancer.