Advancing Trials for HER2+ Breast Cancer With Leptomeningeal Metastasis

Barbara O’Brien, MD, associate professor of neuro-oncology at MD Anderson Cancer Center, discusses the next steps of the phase 2 TBCRC049 study (NCT03501979), which is assessing tucatinib (Tukysa) given in combination with trastuzumab (Herceptin) and capecitabine for the treatment of patients with HER2-positive breast cancer and leptomeningeal metastasis.¹

O’Brien continues the conversation by discussing how trials can be better designed to assess patients with leptomeningeal metastasis. She specifically highlights that these patients with brain metastases have previously been excluded from breast cancer clinical trials, and notes the importance of their inclusion moving forward with research.

Transcription:

0:09 | This regimen offers a glimmer of hope, but we would like to do more for our patients in terms of the durability of response. Some considerations include combining tucatinib with other systemic agents or intrathecal agents and also further consideration of the sequencing of this drug regimen with other options for patients with leptomeningeal metastasis.

0:35 | Historically, patients with brain metastasis and, by extension, leptomeningeal metastasis have been excluded from breast cancer trials, in part because this is a unique subset of patients with breast cancer and there are certain implications in terms of their needs and the response to therapy and the overall survival. But I think it is important that, moving forward, we do include patients with brain metastases such as was done the pivotal HER2CLIMB study². Hopefully, we also have cohorts available for patients with leptomeningeal metastasis and open trials specifically for patients with leptomeningeal metastasis.

REFERENCES:

1. 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

2. Lin NU, Murthy RK, Abramson V, et al. Tucatinib vs placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: updated exploratory analysis of the HER2CLIMB randomized clinical trial [published correction appears in JAMA Oncol. 2023 Feb 1;9(2):284. doi: 10.1001/jamaoncol.2022.7864]. JAMA Oncol. 2023;9(2):197-205. doi:10.1001/jamaoncol.2022.5610