# HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases

Source: https://onco.cc/key-papers/paper-her2climb-nejm-2020/  
OnCo record `paper-her2climb-nejm-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding the brain-penetrant HER2 pill tucatinib to trastuzumab and capecitabine lengthened survival in heavily pretreated HER2-positive metastatic breast cancer, and uniquely the trial included patients with active brain metastases, who also benefited.

## Summary

Phase 3 placebo-controlled trial of 612 patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab and T-DM1, randomised 2:1 to tucatinib or placebo with trastuzumab and capecitabine; nearly half had brain metastases, including untreated or progressing lesions.

Overall survival at two years was 44.9 percent with tucatinib against 26.6 percent with placebo (hazard ratio 0.66); progression-free survival among patients with brain metastases at one year was 24.9 versus 0 percent.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2020
- DOI: 10.1056/NEJMoa1914609
- Authors: Murthy RK, Loi S, Okines A, et al.
- Findings: Two-year overall survival 44.9 percent vs 26.6 percent; hazard ratio for death 0.66.; One-year progression-free survival in patients with brain metastases 24.9 percent vs 0 percent.
- What it means: Tucatinib-based therapy is the standard for HER2-positive disease with active brain metastases and a standard later-line option overall; it was the first trial to enrol progressing brain metastases and show a systemic drug helps them.
- Caveats: Diarrhoea and liver enzyme rises were more frequent with tucatinib.; Trial predates trastuzumab deruxtecan as second-line standard.

## Sources

- N Engl J Med 2020: https://doi.org/10.1056/NEJMoa1914609
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31825569/

## Connected records

- cancers: [HER2-positive breast cancer with brain metastases](https://onco.cc/cancers/her2-positive-breast-brain-metastases/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Tucatinib](https://onco.cc/drugs/tucatinib/)
- trials: [HER2CLIMB](https://onco.cc/trials/her2climb/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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