T-DM1 Aids Patients with Advanced Breast Cancer

Genentech's HER2-targeted antibody–drug conjugate T-DM1 (ado-trastuzumab emtansine; Kadcyla) improves progression-free survival (PFS) in heavily pretreated breast cancer patients with advanced HER2-positive disease, according to results from the phase III TH3RESA trial announced at the 2013 European Cancer Congress on September 28 in Amsterdam, the Netherlands.

“T-DM1 nearly doubled the PFS compared to standard treatment, and there was also a strong trend towards improved overall survival,” says lead investigator Hans Wildiers, MD, PhD, adjunct head of clinic in the department of medical oncology at the University Hospitals Leuven in Gasthuisberg, Belgium.

The TH3RESA trial enrolled 602 women whose cancers were inoperable or had recurred or metastasized after at least two previous treatment regimens involving taxanes, trastuzumab (Herceptin; Genentech), and lapatinib (Tykerb; GlaxoSmithKline).

All patients were randomized to receive either T-DM1, which links trastuzumab with the cytotoxic agent mertansine, or a treatment of their physician's choice (TPC), which primarily involved a chemotherapy/trastuzumab combination.

Results showed that median PFS was 6.2 months for patients receiving T-DM1 compared with 3.3 months for the TPC arm. Among the T-DM1 patients, 31.3% showed a response to the drug, compared with 8.6% of TPC patients. Wildiers says an interim analysis of overall survival (OS) showed 45% fewer deaths in the T-DM1 arm. However, whether the OS benefit is statistically significant probably won't be known until 2015. Patients in the TPC group whose disease progressed were given the option of crossing over to the T-DM1 arm.

The data affirm results from the EMILIA study, which led to the U.S. Food and Drug Administration approval of T-DM1 for use in HER2-positive patients previously treated with trastuzumab and a taxane.

“EMILIA and TH3RESA together allow us to conclude that T-DM1 should become the new standard for patients with HER2-positive metastatic breast cancer after failure of taxane and trastuzumab,” notes Wildiers. He adds that the new data indicate that T-DM1 could also benefit women who have had multiple treatments and would otherwise receive palliative care only.

In addition to improved efficacy, Wildiers says, during the TH3RESA trial T-DM1 produced fewer high-grade toxicities overall, fewer dose reductions and treatment discontinuations, and fewer cases of high-grade diarrhea, neutropenia, and febrile neutropenia compared to standard therapies. However, more cases of thrombocytopenia were reported with T-DM1, an issue that has been noted in the past.

Additional studies looking at T-DM1 are under way, including the MARIANNE Trial, which is evaluating the use of the drug alone and in combination with pertuzumab (Perjeta; Genentech) in patients with previously untreated, metastatic HER2-positive breast cancer.