Stockholm, Sweden—Trastuzumab emtansine (T-DM1), a novel monoclonal antibody–guided therapy for HER2- positive metastatic breast cancer, achieved almost a 40% reduction in the risk of disease progression compared with standard treatment with trastuzumab (Herceptin) and docetaxel (Taxotere), investigators reported at the 2011 European Multidisciplinary Cancer Congress.
Excitement over T-DM1 has been steadily building since early results were presented several years ago. The results have been so encouraging that the manufacturer has a number of similar compounds in development, investigators said.
T-DM1 is an antibody-drug conjugate that links a cytotoxic agent (maytansine) to a monoclonal antibody. It is only when the molecule binds to the HER2 receptor via the antibody and is absorbed into the tumor cell that the chemotherapy is released, producing a highly targeted blow and sparing normal tissues, thus avoiding adverse effects typically associated with chemotherapy, explained Sara Hurvitz, MD, University of California, Los Angeles, who presented the findings of the phase 2 trial.
The study included 137 women with locally advanced or metastatic HER2-positive breast cancer and no prior treatment for advanced disease. They were randomized to 3.6 mg/kg of T-DM1 or to the standard regimen of trastuzumab plus docetaxel.
Progression-free survival (PFS) was 14.2 months with T-DM1 compared with 9.2 months with standard therapy—a 41% relative risk reduction (P = .035), Dr Hurvitz reported.
Although response rates were similar, the median duration of response was markedly higher in the experimental arm. Patients receiving standard therapy were stable for 9.5 months, on average, but the median duration of response had not been reached in the T-DM1 arm at the time of analysis. This means the treatment “is probably very durable,” Dr Hurvitz said.
Patients receiving T-DM1 also were able to remain on treatment much longer than those on standard therapy, primarily because of toxicities such as neuropathy, she pointed out.
Overall toxicity was far lower with T-DM1, which is a key reason for its appeal, Dr Hurvitz suggested. Adverse events were reported by 46.4% of patients taking T-DM1 versus 89.4% of patients receiving standard treatment; discontinuation occurred in 7.2% versus 28.8%. Neutropenia, alopecia, diarrhea, and edema were also substantially less common with T-DM1.
However, thrombocytopenia was observed more often with T-DM1 than with placebo (30.4% vs 6.1%, respectively), and liver enzymes were increased (39.1% vs 6.1%); thrombocytopenia is likely tied to the drug’s effect on the bone marrow, Dr Hurvitz suggested.
The results of 2 ongoing phase 3 trials— EMILIA/TDM4370g and MARIANNE— are expected in spring 2012. Martine Piccart-Gebhart, MD, PhD, of the Jules Bordet Institute, Brussels, Belgium, cautioned that these are early-phase results. Pending the results from the phase 3 trials, however, T-DM1 “hopefully will be available to patients in the not-too-distant future,” she predicted.