AMSTERDAM – Ado-trastuzumab emtansine nearly doubled the time to disease progression for women with heavily pretreated, HER2-positive metastatic breast cancer compared with physician’s choice of treatment in the open-label, phase III TH3RESA trial.
Median progression-free survival was 6.2 months with ado-trastuzumab emtansine (Kadcyla), previously known as T-DM1, and 3.3 months with a treatment of physician’s choice (hazard ratio 0.528; P less than .0001).
Courtesy European CanCer Organisation
Dr. Hans Wildiers
Physician’s choice included chemotherapy and trastuzumab (Herceptin) (68.5%), lapatinib and trastuzumab (10.3%), chemotherapy and lapatinib (2.7%), and hormonal therapy and trastuzumab (1.6%).
An interim overall survival analysis also favored T-DM1 (median not reached vs. 14.9 months; HR 0.552; P = .0034), with the final analysis expected in 2015, Dr. Hans Wildiers said in a presidential session at the multidisciplinary European cancer congresses.
The data reaffirm results from the phase III EMILIA trial, demonstrating a consistent benefit with T-DM1 in previously treated human epidermal growth factor receptor 2–positive (HER2-positive) advanced breast cancer.
"In my opinion, combining EMELIA and TH3RESA, T-DM1 should become the standard of care," he added.
As previously reported, EMILIA showed a 5-month gain in overall survival with T-DM1 over capecitabine (Xeloda) plus lapatinib (Tykerb) in relapsed, metastatic breast cancer.
This led to the approval of T-DM1 in February 2013 in the United States for the treatment of HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. T-DM1 is expected to gain European Union approval by the end of the year, according to Genentech, which markets the drug.
Notably, a total of 80.4% of patients in that arm received a regimen containing trastuzumab.* Median progression-free survival (PFS) in this subgroup was significantly extended by 3 months with T-DM1 compared with physician’s choice (3.2 vs. 6.2; HR 0.558; P less than .001), said Dr. Wildiers of University Hospitals Leuven, Belgium.
Commenting on the results, invited discussant Dr. Clifford Hudis, chief of breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York, said he is optimistic T-DM1 will deliver an overall survival advantage because prior research has shown that a small incremental improvement in PFS, measured in weeks, can lead to an improvement in months in overall survival simply by reintroducing trastuzumab (J. Clin. Oncol. 2012;30:2585-92).
Dr. Clifford Hudis
"A definitive and clinically meaningful overall survival may just be what some markets need to bless this approach, but cost will be an issue," he said. "Arguably, we’re more willing to tolerate the higher cost when overall survival is improved, but even without it, I would see the toxicity advantage as worth a lot."
Patients treated with T-DM1 were less likely than were those given their physician’s choice to reduce dosage (9.4% vs. 19.6%) or stop treatment due to an adverse event (6.7% vs. 11%), Dr. Wildiers said. Grade 3 or higher adverse events were also lower with T-DM1 (32.3% vs. 43.5%).
Significantly more women also responded to T-DM1 than to their physician’s choice (31.3% vs. 8.6%; P less than .001). Further, analyses showed "a clear and consistent effect" that T-DM1 was better across all subgroups, he said.
When pressed by the audience on how T-DM1 should be used in clinical practice, Dr. Wildiers said T-DM1 should likely be reserved for the second-line setting until results are known from the ongoing MARIANNE trial. The phase III trial is evaluating T-DM1 with pertuzumab (Perjeta) versus trastuzumab plus a taxane in women with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer.
Dr. Wildiers reported serving on an advisory board for Roche. His coauthors disclosed ties with several firms, including employment with Genentech, which markets ado-trastuzumab emtansine.
*CORRECTION, 10/10/13: A previous version of this story did not clearly describe the patients who received trastuzumab in the physician's choice arm of TH3RESA.