John Strickler, A. Cercek, Salvatore Siena, Thierry Andre, K. Ng, Eric Van Cutsem, C. Wu, Andrew Scott Paulson, Joleen M. Hubbard, Andrew L. Coveler, C. Fountzilas, Adel Kardosh, Pashtoon Murtaza Kasi, Heinz-Josef Lenz, Kristen Keon Ciombor, Elena M Elez, David L. Bajor, Chiara Cremolini, Federico Sanchez, Mina Nayeri, Wentao Feng, Mark Bieda, Tanios S. Bekaii-Saab
MOUNTAINEER was a multicenter, open-label, phase 2 trial (NCT03043313) that evaluated the efficacy and safety of tucatinib plus trastuzumab, a dual HER2-targeted chemotherapy-free regimen. Patients were included if they had chemotherapy-refractory, HER2+, RAS wild-type unresectable or metastatic colorectal cancer. This final analysis reports updated efficacy and safety after a median follow-up of 32.4 months. Of the 84 patients who received tucatinib plus trastuzumab, the confirmed objective response rate was 39.3%; median duration of response was 15.2 months. Median progression-free survival was 8.1 months and overall survival was 23.9 months. Efficacy was relatively similar across central HER2+ testing methods. No clear association of treatment response with co-occurring biomarker alterations was seen. Few patients discontinued treatment due to adverse events; no treatment-emergent deaths occurred. Tucatinib plus trastuzumab showed clinically meaningful efficacy and favorable safety. Efficacy was observed irrespective of central HER2+ testing methods and in patients with heterogeneous tumor biomarker profiles. The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.