CHICAGO — Women with HER-2–positive breast cancer experienced significantly improved PFS when treated with the investigational agent trastuzumab emtansine compared with standard therapy, according to results of the phase 3 EMILIA study.
Trastuzumab emtansine (T-DM1, Genentech), an experimental antibody-drug conjugate, also has very little dose-limiting toxicity, said researcher Kimberly L. Blackwell, MD, professor of medicine and assistant professor of radiation oncology at Duke Cancer Institute at Duke University.
“For patients facing metastatic breast cancer, this is a breakthrough,” Blackwell said.
Blackwell and colleagues randomized 978 patients to receive either T-DM1 — which has not received FDA approval and is not available outside clinical trials — or the standard therapy of capecitabine (Xeloda, Genetech) and lapatinib (Tykerb, GlaxoSmithKline).
The groups were balanced for baseline demographics and disease characteristics. All patients had received prior treatment with taxane therapy and trastuzumab (Herceptin, Genentech).
The patients assigned to T-DM1 received 3.6 mg/kg IV every 3 weeks. The patients assigned to standard therapy received capecitabine 1,000 mg/m2 orally twice daily on days 1 through 14 every 3 weeks and lapatanib 1,250 mg orally daily.
Treatment continued until disease progression or toxicities became unmanageable.
The primary endpoints were PFS by independent review, OS and safety.
Median follow-up was 12.9 months in the T-DM1 group and 12.4 months for the standard therapy group.
Median PFS among patients assigned to T-DM1 was 9.6 months, compared with 6.4 months for patients assigned to standard therapy (HR=0.65; 95% CI, 0.549-0.771; P<.0001). The difference was statistically significant, the researchers said.
Patients assigned to T-DM1 had higher 2-year survival (65.4% vs. 47.5%), according to an interim analysis. They also demonstrated higher objective response (43.6% vs. 30.8%).
Patients assigned to standard therapy experienced higher rates of grade-3 or higher adverse events (57% vs. 40.8%). Patients in the standard therapy group reported more diarrhea (20.7% vs. 1.6%); hand-foot syndrome (16.4% vs. 0); and vomiting (4.5% vs. 0.8%).
The most common grade-3 or higher adverse events for patients assigned to T-DM1 were thrombocytopenia (12.9% vs. 0.2%) and elevations in liver function tests (aspartate transaminase, 4.3% vs. 0.8%; and alanine transaminase, 2.9% vs. 1.4%). The side effects subsided when patients stopped treatment.
“T-DM1 is a brand new way of treating HER-2–positive breast cancer, and I think it is the first of many antibody drug conjugates to follow that will link a potent anti-cancer agent to a targeted delivery system of an antibody,” Blackwell said during a press conference. “I think this will offer a very important therapeutic option for patients faced with HER-2–positive breast cancer.”
For more information:
Blackwell KL. Abstract #LBA1. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: The researchers report serving as consultants or advisers for, receiving honoraria from, or holding employment or leadership positions with Amgen, Genentech, GlaxoSmithKline, Novartis, Pfizer, Roche and Sanofi.