Kadcyla™ (ado-trastuzumab emtansine, formerly known as T-DM1) extends progression-free survival in women with advanced HER2-positive breast cancer that progressed on two or more previous HER2-directed therapies, according to the results of a study presented at the ESMO 2013 Congress of the European Society for Medical Oncology in Amsterdam.
HER2 is a protein involved in normal cell growth. Approximately 20-25% of breast cancers overexpress (make too much of) the HER2 protein, and this over-expression contributes to cancer cell growth and survival. HER2-targeted therapies such as Herceptin have dramatically improved outcomes for women with HER2-positive breast cancer, but researchers continue to explore new approaches to treatment.
Kadcyla is part of a new class of drugs called antibody-drug conjugates, which consist of an antibody attached to a toxic chemotherapy. It combines Herceptin and a chemotherapy drug (emtansine or DM1) that interferes with cancer cell growth. Kadcyla delivers Herceptin and DM1 directly to HER2-positive cells, and limits exposure of the rest of the body to the chemotherapy.
After more than two HER2-directed treatment regimens for metastatic breast cancer, there is no clear standard of care for patients with progressive disease. TH3RESA is a phase 3 study that included 602 patients with advanced breast cancer previously treated with at least two HER2-directed therapies. Patients were randomly assigned in a 2:1 ratio to Kadcyla or physician’s choice of chemotherapy (83% received Herceptin-based regimens and 17% received chemotherapy). Treatment was continued until disease progression, at which point patients were allowed to crossover to Kadcyla.
Patients in the Kadcyla group had a median progression-free survival of 6.2 months—nearly double that of the patients in the control arm (3.3 months). This was a highly significant difference in favor of Kadcyla. A pre-specified subgroup analysis showed a consistent, near-doubling of progression-free survival with Kadcyla regardless of subgroup (age, geographic area, race, performance status, tumor characteristics, and visceral disease).
Median overall survival has not yet been reached in the Kadcyla group; median overall survival was 40.9 months in the control group. This suggests that there may be a survival advantage for Kadcyla, but long-term confirmation is needed. Final survival results are expected in 2015.
Adverse events of grade 3 or higher were more frequent in the control group (43.5%) than in the Kadcyla group (32.3). Adverse events leading to discontinuation of therapy occurred in 10.9 percent of controls compared with 6.7 percent of the Kadcyla group.
The researchers concluded that Kadcyla resulted in a statistically significant improvement in progression-free survival, with fewer grade 3 adverse events than other treatments in patients previously treated with two or more HER2-directed regimens for HER2-positive metastatic breast cancer.
Wildiers H, Kim SB, Gonzalez-Martin A, et al. T-DM1 for HER2-positive metastatic breast cancer (MBC): Primary results from TH3RESA, a phase 3 study of T-DM1 vs treatment of physician’s choice. Presented at the 38th Congress of the European Society for Medical Oncology (ESMO), Amsterdam, Netherlands, September 27-October 1, 2013. Abstract 15.
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