O’Brien on the TBCRC049 Trial in HER2+ Breast Cancer

Barbara O’Brien, MD, associate professor of neuro-oncology at MD Anderson Cancer Center, discusses the background behind the phase 2 TBCRC049 study (NCT03501979) investigating the combination of tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine for the treatment of patients with HER2-positive breast cancer and leptomeningeal metastasis.

Currently, the combination of tucatinib, trastuzumab, and capecitabine is approved for the treatment of patients with metastatic HER2-positive breast cancer, with or without brain metastases. These patients must have received at least 1 prior HER2-based regimen in the metastatic setting.

TBCRC049, an investigator-initiated phase 2 trial, is assessing a regimen consisting of tucatinib, trastuzumab, and capecitabine in adult patients with HER2-positive breast cancer and newly diagnosed leptomeningeal metastasis. Those enrolled in the trial were those with a Karnofsky performance status > 50 and untreated leptomeningeal metastasis. Patients received the combination in 21-day cycles.

Here, O’Brien discusses the unmet needs commonly seen among the patient population this study focused on and the overall goals of the study, including evaluating the primary end point of overall survival.

Transcription:

0:09 | The study population is patients with leptomeningeal metastasis. Leptomeningeal metastasis is associated with neurologic decline and a very poor prognosis, and we have no standard treatment options. We have a great need for clinical trials and better options for our patients.

0:28 | Our study evaluated the HER2-directed [tyrosine kinase inhibitor] tucatinib, trastuzumab, and capecitabine in patients with HER2-positive breast cancer and leptomeningeal metastasis that was newly diagnosed. Our primary end point was overall survival. We were also looking at [cerebrospinal fluid (CSF)], pharmacokinetics, as well as response assessment, symptoms, and quality of life.

REFERENCE:

O’Brien B, Murthy R, Berry A, et al. Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results. J Clin Oncol. 2024;42(suppl 16): abstr 2018. doi:10.1200/JCO.2024.42.16_suppl.2018