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Tracing Tucatinib's Role in HER2+ Breast Cancer Treatment

Caroline Seymour
Published: Thursday, Jun 14, 2018

Rashmi K. Murthy, MD, MBE

Rashmi K. Murthy, MD, MBE
In a retrospective pooled analysis of tucatinib in phase Ib studies in HER2-positive breast cancer presented at the 2018 Annual ASCO Meeting, Rashmi K. Murthy, MD, reported that patients with isolated brain metastasis progression benefited from CNS-directed therapy and continuation of systemic treatment.1

at the 2018 Annual ASCO Meeting, Murthy discussed the clinical benefit of tucatinib after isolated brain progression in patients with HER2-positive breast cancer.

OncLive: What was the background to this analysis and what prior data were available with tucatinib?

Murthy: Tucatinib is a novel potent HER2-specific TKI that is being developed for the treatment of patients with metastatic HER2-positive breast cancer. It has been studied in combination studies, both with T-DM1 as well as trastuzumab and capecitabine. In the phase Ib study of tucatinib, trastuzumab, and capecitabine that was published online in The Lancet Oncology, the response systemically was 61% and the response in the CNS was 42%.

Why is this a unique agent for patients with HER2-positive breast cancer?

Tucatinib selectively and potently inhibits HER2. Unlike other TKIs in its class, it has less inhibition of EGFR. Therefore, we don't generally see significant EGFR-like toxicities that we see with other TKIs, such as diarrhea and rash. Additionally, in preclinical models, it has been shown to be synergistic with trastuzumab as well as with other agents. It has also shown preclinical CNS activity in patient-derived intracranial xenograft models.

You mentioned its tolerability. What toxicities are associated with tucatinib?

The drug is relatively well tolerated in both the initial monotherapy study, as well as in the more recent combination studies. The main adverse events have been limited to low-grade toxicities—diarrhea, gastrointestinal toxicities like nausea and vomiting, hand-foot syndrome, and fatigue.

What did you find in the retrospective pooled analysis?

In the retrospective analysis presented at the 2018 ASCO Annual Meeting, we pooled 2 phase Ib studies of tucatinib. One was in combination with T-DM1 and the other was in combination with capecitabine and trastuzumab. We identified a subgroup of patients who experienced isolated progression in the brain. Among those patients, we further subdivided them into those who continued on CNS-directed therapy and study treatment and those who discontinued therapy.
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