Tucatinib plus trastuzumab in chemotherapy-refractory metastatic colorectal cancer

The final analysis of MOUNTAINEER trial, recently published on Nature Communications shows that in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer, the combination of tucatinib plus trastuzumab has clinically meaningful efficacy and favorable safety.

The MOUNTAINEER trial is a global, open-label, phase 2 study that enrolled adult patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites in five countries. The trial was designed as a single-cohort study with an expansion and 117 patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days, cohort A) for the duration of treatment until progression; after expansion, patients were randomly assigned to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The final analysis of results, after a median follow-up of 32.4 months, showed a  confirmed objective response rate of 39.3% for the 84 patients who received tucatinib plus trastuzumab; median duration of response was 15.2 months, median progression-free survival was8.1 months and overall survival was 23.9 months. As authors conclude, «Tucatinib and trastuzumab showed durable and clinically meaningful efficacy that can be achieved with a dual HER2-targeted chemotherapy-free strategy.

Efficacy was observed irrespective of central HER2+ testing methods and heterogeneous tumor biomarker profiles. This analysis supports further investigation of tucatinib in combination with trastuzumab in earlier lines of therapy and the phase 3 MOUNTAINEER-03 trial has been initiated towards this goal».