Charles E. Geyer, Jr, MD
Ado-trastuzumab emtansine (T-DM1; Kadcyla) has the potential to transform the way that HER2-positive breast cancer is treated, said Charles E. Geyer, Jr, MD, following the data from the phase III KATHERINE trial.
, Geyer, who is lead study author of the KATHERINE trial, discussed the clinical implications of the KATHERINE trial and the outlook for T-DM1 in patients with HER2-positive breast cancer.
OncLive: Please provide some background on the KATHERINE study.
: KATHERINE was a global phase III trial conducted by investigators committed to [exploring the use of] neoadjuvant therapy in HER2-positive breast cancer as the optimal way to treat their patients, but also as a way to identify high-risk patients. This was a trial to determine if T-DM1 might help the subset of patients who do not achieve pCR who are at a higher risk of recurrence rather than continuing their HER2-targeted therapy for 1 year.
What was the rationale for using T-DM1?
T-DM1 seemed to be the obvious choice, because we know that the drug was approved by the FDA and is active for patients with metastatic disease who had prior exposure to taxanes and HER2-targeted therapy. We wanted to find a drug that would probably work in patients with early breast cancer who had less than an optimal response to these prior therapies.
What was the design of the trial?
The design was straightforward; we did not enter patients at the point where they started their neoadjuvant therapy. With it being a global study, we knew that there would be several different regimens. The study was designed to accrue patients who received neoadjuvant therapy and achieved other standards. They had to have 6 cycles total of chemotherapy and at least 9 weeks each of trastuzumab and a taxane; they also had to have residual invasive breast cancer. We felt like that covered the “waterfront” of standard regimens. They also had to have residual invasive breast cancer. It was a pretty broad net of patients and we put some heterogeneity into the study, which is a strength of it.
What were the findings?
Our primary endpoint was iDFS. We saw a hazard ratio (HR) of 0.5 for patients who had been receiving T-DM1; that is a full 50% in iDFS events for these patients. With that information, they then suggested we publish the results, but more importantly, conduct a full analysis so we can better understand these data sets.
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