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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Editorial - January 3, 2014

Case Study: Lower-Risk Myelodysplastic Syndromes

At the 2013 conference of the Global Biomarkers Consortium, which took place October 4-6, 2013, in Boston, Massachusetts, Rami Komrokji, MD, from the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, discussed the use of personalizing therapy in the management of myelodysplastic syndromes. Myelodysplastic syndromes (MDS) are a [ Read More ]