Tucatinib plus trastuzumab for chemotherapy-refractory, HER2+, RAS wild-type metastatic colorectal cancer (MOUNTAINEER): Final analysis

Authors

• John H. Strickler, Duke University Medical Center, Durham, NC, USA.
• Andrea Cercek, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
• Salvatore Siena, Università degli Studi di Milano, Milan, Italy.
• Thierry André, Department of Medical Oncology, Sorbonne University, Saint-Antoine Hospital, AP-HP, Paris, France.
• Kimmie Ng, Dana-Farber Cancer Institute, Boston, MA, USA.
• Eric Van Cutsem, University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium.
• Christina Wu, Mayo Clinic, Phoenix, AZ, USA.
• Andrew Scott Paulson, Texas Oncology/The US Oncology Network, Dallas, TX, USA.
• Joleen M. Hubbard, Mayo Clinic, Rochester, MN, USA.
• Andrew L. Coveler, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.
• Christos Fountzilas, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
• Adel Kardosh, OHSU Knight Cancer Institute, Portland, OR, USA.
• Pashtoon Murtaza Kasi, Weill Cornell Medicine, New York City, NY, USA.
• Heinz-Josef Lenz, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
• Kristen Ciombor, Vanderbilt University Medical Center, Nashville, TN, USA.
• Elena Elez, Vall d'Hebron University Hospital, Barcelona, Spain.
• David L. Bajor, Case Western Reserve University-University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
• Chiara Cremolini, Azienda Ospedaliero-Universitaria Pisana and Università di Pisa, Pisa, Italy.
• Federico Sanchez, Advocate Health - MidwestFollow
• Mina Nayeri, Pfizer Inc, Bothell, WA, USA.
• Wentao Feng, Pfizer Inc, Bothell, WA, USA.
• Mark Bieda, Pfizer Inc, Bothell, WA, USA.
• Tanios S. Bekaii-Saab, Mayo Clinic Arizona, Phoenix, AZ, USA. Bekaii-Saab.Tanios@mayo.edu.

Recommended Citation

Strickler JH, Cercek A, Siena S, et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 + , RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis. Nat Commun. 2026;17(1):1068. Published 2026 Jan 12. doi:10.1038/s41467-025-67824-z

Abstract

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.

Document Type

Article

PubMed ID

41526345