Tripathy Provides an Overview of the TBCRC049 Study for HER2+ Breast Cancer

Debu Tripathy, MD, professor and chairman of the Department of Breast Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the TBCRC049 study (NCT03501979) which evaluated tucatinib (Tukysa), capecitabine (Xeloda), and trastuzumab (Herceptin) in the cerebral spinal fluid of patients with HER2-positive breast cancer and leptomeningeal disease.

According to findings presented from the TBCRC049 study, patients had consistent ranges of tucatinib and ONT-993 upon analysis and were detectable within 2 hours following the administration of tucatinib.

Further, concentrations ranged from 0.57-25 ng/mL for tucatinib and 0.28-4.7 ng/mL for ONT-993, from cycles 1 to 2. For tucatinib, these concentrations were above the prespecified IC50 levels of tucatinib against HER2 (3.3 ng/mL).

Transcription:

0:08 | The initial thinking of the study was that patients with HER2-positive breast cancer do have a fairly high incidence of developing brain metastases. In patients with metastatic HER2- positive disease, as many as 50% of patients over some course of their treatment are going to experience brain metastases and in some cases, this involves a particularly aggressive form of this known as leptomeningeal disease, which involves the minigenes and typically, one sees positive cancer cells in the cerebrospinal fluid. This tends to have an even worse prognosis than intracranial metastasis.

0:53 | In the HER2CLIMB study, which was the randomized study that led to the approval of the addition of tucatinib to the backbone of capecitabine and trastuzumab and was tested in patients with metastatic breast cancer, it allowed patients with brain metastases, and even allowed patients with untreated brain metastases, who did not receive local treatment but had minimal symptoms. Overall, about half the patients in that study had brain metastases.

1:25 | The results of that study did show that the addition of tucatinib improved progression-free and overall survival. In particular, it improved these outcomes in patients with brain metastases. In the patients that have untreated brain metastases, they actually saw responses in that group of patients. So that study, as well as studies that had preceded the randomized study, even in the phase 1 study of tucatinib, patients with brain metastases were seen to have responses. That led to this study, to test it in a smaller group of patients that have leptomeningeal disease that is HER2-positive.