Final data from the SGNTUC-019 trial support the use of the agent with trastuzumab in heavily pretreated patients
The combination of tucatinib, an oral tyrosine kinase inhibitor, with trastuzumab continues to show clinically meaningful efficacy and durable responses, along with favorable tolerability, in patients with heavily pretreated HER2-mutated metastatic breast cancer (MBC) as reported in the final analysis of SGNTUC-019 (NCT04579380), an open-label phase 2 basket study. Results were presented at the ESMO Breast Cancer 2025, held in Munich, Germany, earlier this month (Abstract 304MO).
Currently, there are no approved treatments for patients with HER2-mutated MBC. Tucatinib is highly selective for HER2 and is already approved for previously treated HER2-positive MBC (combined with trastuzumab and capecitabine) and previously treated HER2 metastatic colorectal cancer (combined with trastuzumab) in certain geographical areas.
With an additional 10 months of follow-up, final analysis results of SGNTUC-019 confirm previously reported findings. In the primary analysis, at a median follow-up of 15 months, confirmed objective response rate (cORR) was 41.9%, with a median duration of response (DOR) of 12.6 months, median progression-free survival was 9.5 months (90% CI: 5.4–13.8) and overall survival (OS) was 20.1 months (90% CI: 15.9 to not estimable) (Nat Med. 2025 Mar;31(3):909-916). At a median follow-up of 24.9 months, cORR (41.9%) was maintained, with a prolonged median DOR of 18.2 months. The median PFS was 10.9 months, and the median OS was 32.7 months.
Overall, the combination therapy was well tolerated, with a low rate of treatment discontinuation (6%) and no deaths due to treatment-emergent adverse events (TEAEs). “We know from the use of tocatinib in the HER2-positive setting that diarrhea is the most common toxicity”, said Dr Cristina Saura Manich, Vall d’Hebron Institute of Oncology, Barcelona, Spain, commenting on the safety results at the congress. “However, we also know that primary prophylaxis can be initiated, and we should implement it.”
“Before these data, the concept of targeting for HER2-mutated breast cancer had been addressed with other TKIs like neratinib, but not all patients included in earlier studies benefitted from these agents”, she noted during the Mini Oral session. “I would like to highlight the message that lobular histology in breast cancer commonly harbours HER2 mutations, as is reflected in the proportion of patients included in the SGNTUC-019 trial. Given a median number of three prior lines in the metastatic setting, the overall response rate achieved in this study is encouraging.”
