T-DM1 Significantly Improves Outcomes in HER2-Positive Breast Cancer

Roxanne Nelson

June 03, 2012

June 3, 2012 (Chicago, Illinois) — The investigational agent trastuzumab emtansine (T-DM1) can improve progression-free survival in some women with metastatic breast cancer.

According to study results presented at the plenary session here at the 2012 Annual Meeting of the American Society of Clinical Oncology, T-DM1 (Roche/Genentech), compared with standard therapy using capecitabine (Xeloda) and lapatinib (Tykerb), significantly improved progression-free survival in women with HER2-positive locally advanced or metastatic breast cancer who had previously been treated with a taxane and trastuzumab.

Median progression-free survival was longer in patients treated with T-DM1 than in those treated with the standard therapy (9.6 vs 6.4 months). This difference reached statistical significance.

Median overall survival for patients treated with T-DM1 was not reached, but median overall survival for those treated with standard therapy was 23.3 months (hazard ratio [HR], 0.621; P = .0005).

"What we have shown is that T-DM1 significantly improves progression-free survival, compared with capecitabine and lapatinib, and there is a strong trend favoring overall survival," said senior author Sunil Verma, MD, chair of breast medical oncology at the Sunnybrook Odette Cancer Centre and assistant professor at the University of Toronto, in Ontario, Canada.

In an interview, Dr. Verma pointed out that "incredible strides" have been made in the treatment of HER2-positive breast cancer using trastuzumab and lapatinib, but that they have to be used with chemotherapy to see the benefit. "The idea with this compound is really precision chemotherapy and to deliver the chemotherapy right to the targeted cells," he explained.

"This is a treatment option for patients with metastatic HER2-positive breast cancer that truly changes what we can offer for them. It should be one of the standards of care available to them," Dr. Verma told Medscape Medical News.

T-DM1 is an antibody–drug conjugate consisting of the antibody trastuzumab (Herceptin) and linked to the cytotoxin mertansine (DM1). It incorporates the antitumor activities of trastuzumab and the HER2-targeted delivery of DM1.

We've taught an old friend a new trick.

"We've taught an old friend a new trick — we're using [trastuzumab] as a delivery vehicle," said Andrew D. Seidman, MD, a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York City who was not involved with the trial.

This is a very exciting time; other agents are also currently in trials, Dr. Seidman told Medscape Medical News.

It has yet to be determined how some of these agents should best be combined, he continued. For example, pertuzumab, which is currently being developed by Genentech, and T-DM1 are being examined together in the MARIANNE trial, which is a first-line study in HER2-positive breast cancer. "They recently completed accrual, so we are going to be hearing more big stories," he said.

"What I'm hearing from the EMILIA trial is that 1 drug...outperforms 2 drugs in terms of cancer progression," Dr. Seidman explained. "This can translate to a survival benefit."

Study Details

The EMILIA trial is a randomized phase 3 international study that compared T-DM1 with capecitabine and lapatinib. It is currently the only approved combination for trastuzumab-refractory HER2-positive metastatic breast cancer.

Dr. Verma and colleagues enrolled 991 patients with confirmed HER2-positive metastatic breast cancer (positive for immunohistochemistry [IHC] 3+ and/or fluorescent in situ hybridization [FISH]) who had been previously treated with trastuzumab and a taxane. The primary end points were progression-free survival, overall survival, and safety.

A total of 978 patients in the cohort received treatment. The median durations of follow-up were 12.9 months in the T-DM1 group and 12.4 months in the standard-therapy group. The baseline demographics, previous therapy, and disease characteristics were balanced between the 2 groups.


Measures T-DMI Standard Therapy
Overall Survival at 1 Year, % 84.7 77.0
Overall Survival at 2 Years, % 65.4 47.5
Objective Response Rate, Months (95% CI) 43.6 (38.6–48.6) 30.8 (26.3–35.7)
Duration of Response in Patients
With Overall Response, Months
12.6 6.5
Adverse Events of Grade 3 or Higher, % 40.8 57.0

The most common adverse events of grade 3 or higher with T-DM1, compared with standard therapy, were thrombocytopenia (12.9% vs 0.2%), increased aspartate aminotransferase (4.3% vs 0.8%), and increased alanine aminotransferase (2.9% vs 1.4%). Patients treated with capecitabine and lapatinib experienced more diarrhea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0.0%), and vomiting (4.5% vs 0.8%) than those treated with T-DM1.

Dose reductions were more common with standard therapy (53.4% for capecitabine and 27.3% for lapatinib.

2012 Annual Meeting of the American Society of Clinical Oncology (ASCO): Abstract LBA1. Presented June 3, 2012.


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