Multinational phase 2 basket trial of tucatinib plus trastuzumab for HER2-mutated metastatic breast cancer

HER2 signaling promotes cell growth and differentiation, and is overexpressed in several tumor types. The multinational phase 2 basket study SGNTUC-019 evaluates the combination of tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2-altered solid tumors. Results in the cohort of patients with metastatic breast cancer (mBC) have now been published. The median number of previous lines of therapy in any setting was 4 (range 1-10) and 3 (1-7) in the advanced setting. The overall response rate to tucatinib plus trastuzumab (plus fulvestrant in HR-positive mBC patients) was 41.9% (90% CI 26.9 -58.2) with median duration of response 12.6 months (90% CI 12.6 months) and responses across various HER2 mutations. The median progression-free and median overall survival were 9.5 months (90% CI 5.4-13.8) and 30.1 months (15.9-NE). There were no new safety signals. The authors conclude that the chemotherapy-free regimen of tucatinib and trastuzumab showed clinically meaningful antitumor activity with durable responses and favorable tolerability in pretreated patients with HER2-mutated mBC.