T-DM1 Extends Survival in HER2+ Breast Cancer

According to results from the phase III TH3RESA study, the antibody–drug conjugate ado-trastuzumab emtansine (Kadcyla; Roche)—commonly called T-DM1—increases overall survival (OS) in patients with metastatic HER2-positive (HER2+) breast cancer who have already received multiple treatments. The data were presented by Hans Wildiers, MD, PhD, a medical oncologist at the University of Leuven in Belgium, during the 2015 San Antonio Breast Cancer Symposium in Texas, held December 8–12.

T-DM1's 2013 approval was based on the phase III EMILIA study, in which enrolled patients—all previously treated with trastuzumab (Herceptin; Roche) or taxane chemotherapy—had a considerably longer median progression-free survival (PFS) and OS on T-DM1, compared with those who received lapatinib (Tykerb; GlaxoSmithKline) plus capecitabine (Xeloda; Roche).

“The goal of TH3RESA was to investigate T-DM1 in a still more advanced patient population, compared to EMILIA,” Wildiers explained. The study's 602 participants had all been on prior regimens that included a taxane and two or more HER2-directed therapies, including trastuzumab and lapatinib. They were randomized to receive T-DM1 or treatment of physician's choice (TPC)—the latter being “a pragmatic approach that's increasingly used” as a control in clinical trials where there are multiple, equally reasonable courses of action and no consensus standard therapy, Wildiers said. He noted that approximately 80% of patients in the TPC arm were given trastuzumab-containing regimens, and because crossover to the other arm was allowed upon disease progression, at least 50% eventually received T-DM1.

Patients treated with T-DM1 had a median OS of 22.7 months, compared with 15.8 months for those given TPC, Wildiers reported. He called this gain of nearly 7 months “highly significant, because there are several breast cancer therapies that increase PFS but not OS, and these patients urgently need new options.” The OS benefit seen with T-DM1 was virtually unchanged in a follow-up sensitivity analysis, which excluded patients who switched from TPC to T-DM1.

Consistent with other studies, T-DM1's toxicity profile was favorable, with thrombocytopenia being its main side effect. Overall, the frequency of adverse events, notably diarrhea, was higher in the TPC arm. While quality of life was not formally assessed, “it appears to be acceptable in many of the patients I see daily,” Wildiers said.

“I think the clinically meaningful data obtained with TH3RESA, along with that of EMILIA, solidify T-DM1's therapeutic role in advanced, heavily pretreated HER2+ breast cancer,” he added.

“To put these results in perspective, we used to hate diagnosing HER2+ breast cancer in patients, thinking it was one of the more aggressive forms,” said Kent Osborne, MD, director of Baylor College of Medicine's Cancer Center in Houston, TX. “Now, with effective targeted therapies available, it's actually turned out to be a good disease subtype to have.” –Alissa Poh