T-DM1, a combination drug of trastuzumab and a cell-killing drug emtansine, significantly improved progression-free survival in women with advanced HER2-positive breast cancer whose cancer has recurred or progressed despite previous treatments, according to the results of the TH3RESA trial.
“In TH3RESA, T-DM1 demonstrated improved efficacy and safety compared with treatment of physician’s choice,” Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, told Cancer Network.
These results reaffirm results from the EMILIA study that demonstrated a consistent benefit with T-DM1 in patients with previously treated HER2-positive advanced breast cancer.
“To date, T-DM1 has thus demonstrated clear superiority in two large phase III studies, and should become the new standard for women with HER2-positive breast cancer who were previously treated with a regimen containing a taxane and trastuzumab,” said Wildiers, who presented the results at the 2013 European Cancer Congress in Amsterdam.
TH3RESA was an international phase III trial that included 602 patients with cancer that was inoperable or had recurred or metastasized after several prior treatments including trastuzumab and lapatinib. The patients were randomly assigned 2:1 to receive 3.6 mg/kg intravenous T-DM1 every 3 weeks or treatment of physician’s choice, which consisted of HER2-directed regimens (83.2%) or single-agent chemotherapy (16.8%).
“There was a significant improvement in progression-free survival with T-DM1, and the interim overall survival analysis favored T-DM1 but did not cross the efficacy stopping boundary at the time of this analysis,” Wildiers said.
Specifically, progression-free survival for patients assigned T-DM1 was 6.2 months compared with 3.3 months for patients assigned physicians’ choice. In addition, 31.3% of patients assigned T-DM1 showed a response to the drug compared with only 8.6% of patients assigned to a treatment of physicians’ choice.
“There were fewer grade ≥ 3 adverse events with T-DM1 compared with physicians’ choice, and fewer discontinuations and dose reductions due to adverse events,” Wildiers said.
More grade 3 thrombocytopenia was reported in patients assigned T-DM1 (4.7% vs 1.6%). More grade 3 neutropenia, febrile neutropenia, and diarrhea were reported in patients assigned to physicians’ choice of treatment.
To date, 44 patients have crossed over from the physicians’ choice arm to treatment with T-DM1.
“This trial will continue until the final overall survival analysis takes place or until the survival benefit for treatment with T-DM1 reaches statistical significance at an interim analysis,” Wildiers said in a press release. “T-DM1 is also being tested both alone and in combination with pertuzumab in patients with previously untreated HER2 positive metastatic breast cancer in the MARIANNE trial.”