{"entity":{"id":"paper-her2climb-nejm-2020","kind":"paper","name":"HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases","aka":[],"tldr":"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.\n\nOverall 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.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa1914609"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31825569/"}],"tags":[],"related":[],"cancers":["her2-positive-breast-brain-metastases"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine","trastuzumab","tucatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["her2climb"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1914609","pmid":"31825569","authors":"Murthy RK, Loi S, Okines A, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":612},"route":"/key-papers/paper-her2climb-nejm-2020/","neighbours":{"cancer":[{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"trial":[{"id":"her2climb","kind":"trial","name":"HER2CLIMB","route":"/trials/her2climb/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}