The final results of the Phase 2 MOUNTAINEER trial confirm that the combination of tucatinib (Tukysa) and trastuzumab (Herceptin) provides lasting benefit with manageable side effects for patients with HER2-positive, RAS wild-type metastatic colorectal cancer.
After a median follow-up of 32.4 months, the confirmed overall response rate was 39.3%. Median overall survival reached 23.9 months, while median progression-free survival was 8.1 months. The median duration of response was 15.2 months, and 65% of patients experienced tumor shrinkage. Patients who first received tucatinib alone and later switched to the combination also benefited, with a response rate of 28.6%.
The treatment, which does not include chemotherapy, was generally well tolerated. The most common side effects were diarrhea (66.3%), fatigue (44.2%), and nausea (34.9%). Most side effects were mild to moderate, and only 5.8% of patients stopped tucatinib due to adverse events. No treatment-related deaths were reported.
These findings support the FDA’s January 2023 approval of the combination for patients whose cancer progressed after standard chemotherapy. A Phase 3 trial, MOUNTAINEER-03, is now testing the combination with mFOLFOX6 as a first-line treatment to determine whether earlier use can further improve survival.