Safety of T-DM1/Temozolomide for The Prevention of HER2-Breast Cancer Associated Brain Mets

Alexandra S. Zimmer, MD, assistant research physician with the Women's Malignancies Branch at the National Cancer Institute, discusses the safety of the combination of the T-DM1 ado-trastuzumab emtansine (Kadcyla) and temozolomide, for the prevention of further brain metastases in patients with HER2-positive breast cancer with brain metastases.

According to Zimmer, the combination was found to be safe and well tolerated. During the phase 1 study, patients received the T-DM1 at a dose of 3.6mg/kg every 21 days. Temozolomide was developed to prevent new brain metastases. The study followed a 3+3 design and enrolled a total of 12 patients, with a starting dose of 30mg and a maximum dose of 50 mgs.

No major severe adverse events were observed, according to Zimmer. Mainly adverse events were related to lab results such as thrombocytopenia and leukopenia. No febrile neutropenia was observed. An increase in liver function was also seen, according to Zimmer.

0:08 | So we basically found that it's safe to use the combination T-DM1 with temozolomide. What we did was use the T-DM1, the way that we use that standard, which is 3.6 mg/kg every 21 days. What we added to that was the temozolomide to prevent new brain metastases. And these we did in the standard way that we do that, which is a 3+3 design, were you give the initial group of patients a certain dose, which was 30 mg per square meter of temozolomide, which is an oral drug, every day, because that's the way we looked in the preventive setting in the preclinical data.

0:55 | And then what we did was the 30 mg were the first 3 patients then, we increase the dose to 40 mg per square meter of temozolomide in the second group, that will have 3 patients also. And then the final group is 50 milligrams per square meter with 6 patients since this was the final group, we had to confirm that was safe. So, we have a total of 12 patients that were enrolled in this trial. And in terms of toxicity and safety, it was very safe to use. These patients didn't have any major severe side effects, grade 3 or grade 4. The main side effects are related to laboratory findings like thrombocytopenia, leukopenia, no febrile neutropenia or nothing like that. These patients also have an increase in liver function, but all grade 1, maximum grade 2, so nothing that affected really the use of the drugs by these patients.