Tucatinib Detectable in Cerebral Spinal Fluid and Plasma of Patients With HER2+ BC

Erica Stringer-Reasor, MD, an assistant professor of medicine in the division of at the University of Alabama at Birmingham, discusses the results of a phase 2 study (NCT03501979) examining the combination of tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine (Xeloda) in patients with HER2-positive breast cancer with leptomeningeal metastasis.

According to Stringer-Reasor, this combination has been approved by the FDA for the treatment of advanced metastatic HER2-positive breast cancer. This indication is for patients with and without brain metastases. However, no study has evaluated the efficacy of the combination in patients with brain metastases. Patients with brain metastases are often excluded from clinical trials due to the aggressive nature of the disease.

Pharmacokinetic analysis of the agent found that both tucatinib and its parent drug ONT-993 were detected in both the cerebrospinal fluid and were proportional to levels in the plasma. According to the Stringer-Reasor, the study has 18 patients with the hope of accruing 30. 

0:08 | The combination of tucatinib, trastuzumab and capecitabine has been recently FDA approved for the treatment of advanced metastatic HER2-positive breast cancer, in addition to patients diagnosed with brain metastases. But there's been no study to really evaluate this combination in leptomeningeal disease. In fact, in most clinical trials, leptomeningeal disease is often excluded from studies due to its aggressive nature. In this study, we evaluated the first 15 patients and assess the pharmacokinetics in the CSL as well as in the plasma. And what we found is that tucatinib and its parent drug, ONT-993 were detected in both the CSF and were proportional to levels in the plasma. So, to our knowledge, this is the first study to evaluate tucatinib and its parent metabolite in the CSF.

1:08 | Currently, we are at a total enrollment of 18 patients, which we hope to accrue 30 patients to this study. And we hope to evaluate the efficacy and safety of this combination at a later date and report it when all patients have been accrued.