CHICAGO A study of Roche's experimental "armed antibody" found it extended the length of time breast cancer patients lived without their disease getting worse, marking the second successful pivotal trial in this new class of cancer drugs.
The drug, TDM-1, uses Roche's antibody drug Herceptin to deliver a potent cell-killing payload developed by ImmunoGen directly into cancer cells, with the aim of boosting drug response while lowering the risk of side effects.
"TDM-1 is really a magic bullet in that it is designed to use the power of Herceptin to seek out cancer cells and then liberates inside those cells a very powerful drug," said Dr. Louis Weiner, an oncologist and director of the Georgetown Lombardi Comprehensive Cancer Center, who was not involved in the study.
Herceptin, or trastuzumab, is approved for use in the 25 percent or so of breast cancer patients whose tumors generate a protein called HER-2, which can fuel cancer growth.
The Roche trial involved nearly 1,000 patients with advanced or metastatic breast cancer who had already been treated with both a taxane chemotherapy drug and Herceptin. They were given either TDM-1 or a combination of Tykerb, sold by GlaxoSmithKline, and chemotherapy drug Xeloda.
The TDM-1 patients lived for a median of 9.6 months before their disease worsened, compared with 6.4 months for the comparison group.
After two years, 65.4 percent of the T-DM1 patients were alive, compared with 47.5 percent of the Tykerb/Xeloda patients.
"The safety results also favored TDM-1, including time-to-symptom progression," said Dr. Kimberly Blackwell, professor of medicine at Duke University and the study's lead author.
Side effects seen with TDM-1 included low platelet counts and elevated liver enzymes.
Roche aims to file this year for both U.S. and European approval for the new drug, although it is still talking with regulators about whether it will need to have full survival data from the trial before seeking approval.
The company expects a decision by next Friday on its application for U.S. approval of pertuzumab, an antibody designed to bind to a different region of the HER2 receptor.
If both pertuzumab and TDM-1 are approved, HER2-positive breast cancer patients could initially be treated with a combination of pertuzumab, herceptin and chemotherapy, followed by second-line treatment with TDM-1, said Sandra Horning, head of global development at Roche's Genentech unit.
She said the company was currently conducting clinical trials of eight "armed antibodies," but declined to comment on whether any of the trials involved antibodies already on the market as cancer drugs.
"This is a platform. It could potentially be amenable to a variety of different cancers," Horning said, noting that antibodies suitable for use with drug conjugates needed to be highly selective with targets internalized by cancer cells.
Seattle Genetics last year received U.S. approval for Adcentris, a conjugate made up of a tumor-targeting antibody linked to a potent chemotherapy drug. It targets an antigen expressed on Hodgkin's lymphoma, several types of T-cell lymphoma and other hematologic malignancies.
Roche has also licensed Seattle Genetics' technology for its armed antibody programs.
The first U.S.-approved armed antibody, Pfizer's Mylotarg, was pulled from the market in 2010 after a study showed that adding it to chemotherapy did not extend survival for patients with previously untreated acute myeloid leukemia, an aggressive bone-marrow cancer.
"It is likely that we are going to see a whole new generation of these antibody-drug conjugates targeting many different kinds of structures on cancer cells," Dr Weiner said.
(Reporting By Deena Beasley; Editing by Peter Cooney and David Brunnstrom)