December 2013, Vol 2, No 8

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T-DM1 Prolongs Survival in Advanced HER2-Positive Breast Cancer

European Cancer Congress

The antibody-conjugate T-DM1 (Kadcyla, Genentech) prolonged progression-free survival (PFS) in advanced HER2-positive breast cancer in a heavily pretreated population, according to final results from the phase 3 TH3RESA trial. The study included cancer that progressed on 2 or more previous HER2-directed therapies (trastuzumab and lapatinib).

TH3RESA extended the results of the EMILIA trial, in which T-DM1 extended PFS versus capecitabine/lapatinib in HER2-positive advanced breast cancer in women previously treated with trastuzumab and a taxane. T-DM1 was granted FDA approval for previously treated progressive metastatic HER2-positive breast cancer based on EMILIA results.

“In TH3RESA, T-DM1 achieved a significant improvement in PFS, and the effect was clear and consistent across subgroups. These data affirm the results from EMILIA, demonstrating a consistent PFS benefit of T-DM1 in patients with previously treated HER2-positive advanced breast cancer,” said Hans Wildiers, MD, University Hospitals Leuven, Belgium. He presented these results at the 2013 European Cancer Congress.

“T-DM1 should become the new standard of care for second-line treatment,” Wildiers stated.
TH3RESA enrolled 602 patients with advanced breast cancer previously treated with at least 2 HER2-directed therapies and randomized them in a 2:1 ratio to T-DM1 or 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.

Median PFS was 6.2 months for T-DM1 versus 3.3 months in the control arm, representing an almost doubling of PFS in the experimental arm. The PFS difference between groups was highly 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.

Wildiers also presented the first interim analysis of overall survival (OS) from TH3RESA: median OS 14.9 months in the control arm and “not yet reached” for T-DM1. Longer-term follow-up will determine if there is a survival advantage.

No new safety signals for T-DM1 were reported in TH3RESA. Adverse events grade 3 or higher 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% in 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%, respectively.

First-line therapy with T-DM1 is being evaluated in an ongoing phase 3 trial in advanced HER2-positive breast cancer.

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