# Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)

Source: https://onco.cc/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/  
OnCo record `paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A HER2 pill with an antibody gave a 38 percent response rate in chemotherapy-refractory HER2-positive bowel cancer, and became the first HER2-directed regimen approved for the disease.

## Summary

Strickler, Cercek, Siena and colleagues enrolled patients aged 18 and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites in Belgium, France, Italy, Spain and the United States. The study began as a single cohort of tucatinib 300 mg orally twice daily plus intravenous trastuzumab, and after an interim analysis expanded with randomisation 4:3 to the combination or to tucatinib alone. The primary endpoint was confirmed objective response by blinded independent central review in the two combination cohorts together.

Between August 2017 and September 2021, 117 patients were enrolled; 114 had locally assessed HER2-positive disease and received treatment, with a median age of 56.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: The Lancet Oncology
- Year: 2023
- DOI: 10.1016/S1470-2045(23)00150-X
- Authors: Strickler JH, Cercek A, Siena S, et al.
- Findings: Confirmed objective response by central review in the combination cohorts 38.1 percent (95 percent CI 27.7 to 49.3) of 84 patients: three complete and 29 partial responses.; Commonest adverse event in the combination cohorts was diarrhoea (55 of 86, 64 percent); commonest grade 3 or worse event was hypertension (six of 86, 7 percent).; Tucatinib-related serious adverse events in three of 86 patients; no deaths were attributed to adverse events.
- What it means: The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.
- Caveats: Single-arm for the primary endpoint; the randomised monotherapy cohort was small and not the registration basis.; Response rate rather than survival, in a rare biomarker group.; Funded by the manufacturers.

## Sources

- Lancet Oncol 2023: https://doi.org/10.1016/S1470-2045(23)00150-X
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37142372/

## Connected records

- key papers: [Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)](https://onco.cc/key-papers/paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016/), [Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01)](https://onco.cc/key-papers/paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [HER2](https://onco.cc/targets/her2/)
- drugs: [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Tucatinib](https://onco.cc/drugs/tucatinib/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- trials: [MOUNTAINEER](https://onco.cc/trials/mountaineer/)
- people: [Andrea Cercek](https://onco.cc/people/andrea-cercek/), [Eric Van Cutsem](https://onco.cc/people/eric-van-cutsem/), [John H. Strickler](https://onco.cc/people/john-strickler/), [Salvatore Siena](https://onco.cc/people/salvatore-siena/), [Tanios Bekaii-Saab](https://onco.cc/people/tanios-bekaii-saab/), [Thierry André](https://onco.cc/people/thierry-andre/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)

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