Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer

Data from SGNTUC-019 phase 2 basket trial, recently published on Nature Medicine. Show that a chemotherapy-free regimen with tucatinib and trastuzumab has a clinically meaningful antitumor activity with durable responses and favorable tolerability in heavily pretreated patients with HER2-mutated metastatic breast cancer.

SGNTUC-019 is an open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2-altered solid tumor. Thirty-one patients were enrolled in the HER2-mutated metastatic breast cancer cohort; in these patients the overall response rate (primary endpoint) was 41.9%. Duration of response was 12.9 months and progression-free survival was 9.5 months. The combination of tucatinib and trastuzumab, with fulvestrant for hormone receptor positive patients, was well tolerated and consistent with the established safety profile of the combination. «Exploratory biomarker analyses showed responses in patients harboring a variety of HER2 mutations», authors point out. «Limitation of this analysis are the small size of the cohort and lack of a comparator arm. In addition, the duration of follow-up was short; therefore, the overall survival data are immature with relatively few events and should be interpreted with caution». Nevertheless, authors conclude that «the combination of tucatinib and trastuzumab, with fulvestrant in HR+ disease, was well tolerated and clinically active in patients with previously treated HER2-mutated metastatic breast cancer. These results support further investigation of HER2-directed therapies in patients with HER2 mutations».