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FDA Approval: Tucatinib (Tukysa) for Breast Cancer
FDA approved Tucatinib (Tukysa), a HER2 tyrosine kinase inhibitor, for certain people with breast cancer. What was approved, the evidence, and what it does and doesn't mean.
Original commentary from the Cancer Explained editorial team.
Please note: this page is educational only — it is not medical advice, and it does not speculate about anyone’s health beyond reliable public reporting. For questions about your own health, talk with your healthcare team.
The problem of the brain
HER2-positive breast cancer has a particular habit. It travels to the brain more often than most other breast cancers do.
That creates a treatment problem. The blood-brain barrier is a tight lining of cells around the brain's blood vessels that keeps most molecules out. Large antibody drugs such as trastuzumab, the mainstay of HER2 treatment, do not cross it well. So a woman could have her cancer well controlled everywhere in the body except the one place that mattered most.
Tucatinib, sold as Tukysa, was designed against that gap. It is a small molecule, not an antibody, and it blocks the HER2 tyrosine kinase, the switch inside the cell that HER2 uses to signal growth.
What HER2 is
HER2 is a protein on the surface of some breast cancer cells. When a tumor makes far too much of it, the cancer grows faster. Pathologists test every new breast cancer for it, and the result is written on the pathology report as HER2-positive or HER2-negative.
That one letter-and-number changes everything about the plan. HER2-positive disease responds to a whole family of drugs that do nothing at all for HER2-negative disease. Our page on biomarker testing explains how these results are produced.
HER2CLIMB
The FDA approved tucatinib on 17 April 2020 under NDA 213411 from Seagen. The evidence came from HER2CLIMB, published in the New England Journal of Medicine in 2020.
The trial enrolled 612 people with HER2-positive metastatic breast cancer who had already been treated with trastuzumab, pertuzumab and trastuzumab emtansine. Crucially, it did not exclude people with brain metastases, which most trials at the time did. Everyone received trastuzumab and capecitabine; they were randomized to add either tucatinib or placebo.
In the primary analysis of the first 480 people randomized, progression-free survival at one year was 33.1% with tucatinib against 12.3% with placebo. Median progression-free survival was 7.8 months against 5.6 months, with a hazard ratio of 0.54.
Overall survival at two years was 44.9% against 26.6%. Median overall survival was 21.9 months against 17.4 months, with a hazard ratio for death of 0.66.
Among people with brain metastases, one-year progression-free survival was 24.9% with tucatinib and 0% with placebo. Median progression-free survival in that group was 7.6 months against 5.4 months.
What it costs the body
The common side effects in the tucatinib group were diarrhea, hand-foot skin reaction, nausea, fatigue and vomiting. Severe diarrhea and raised liver enzymes were both more common with tucatinib than with placebo.
The current DailyMed label indicates tucatinib in combination with trastuzumab and capecitabine for adults with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have had one or more prior anti-HER2 regimens in the metastatic setting. A separate colorectal cancer indication was added later.
Where this sits in breast cancer overall
American Cancer Society projections, which SEER republishes, give 321,910 new US female breast cancer diagnoses and 42,140 deaths in 2026. Five-year relative survival across all stages, for 2016 to 2022, is 91.9%.
By stage it is 100.0% for localized disease, 87.5% for regional disease in nearby lymph nodes, and 33.8% for distant disease. Sixty-four percent of cases are found while localized; 6% are distant at diagnosis. HER2CLIMB studied that last group, after several earlier treatments had already been used. These are group averages over past years and describe no individual. Our page on breast cancer covers the types.
When to get checked
Screening matters most here, because HER2-positive disease found early is treated very differently from disease found late. Between mammograms, bring these to a doctor:
- A new lump or firm area in the breast or under the arm
- A change in breast size or shape
- Nipple discharge that is not milk, or a nipple that turns inward
- Skin that dimples, puckers, reddens or becomes scaly
- After a breast cancer diagnosis: new headaches, vision changes, unsteadiness, seizures or new weakness on one side
That last line matters for anyone living with HER2-positive disease. Brain metastases are treatable, and finding them early widens the options.
What this does not mean
- Tucatinib is for HER2-positive disease. HER2-negative breast cancer will not respond to it.
- The trial studied people already treated with three HER2 drugs. It does not describe first-line treatment.
- Median gains were measured in months, not years, in a heavily pretreated group. The brain-metastasis result was the striking part.
- Diarrhea and liver enzyme rises were more frequent with tucatinib. Tolerability is part of the decision.
- The DailyMed label, not this page, is the authority on who the drug is for, and it changes as new data arrive.
Sources
- New England Journal of Medicine (record via PubMed), Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer (HER2CLIMB) — https://pubmed.ncbi.nlm.nih.gov/31825569/
- DailyMed, TUKYSA (tucatinib) label — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f27eb1b9-b7fc-424e-988f-84dd7bb195a3
- FDA Drugs@FDA (openFDA API), TUKYSA NDA 213411, approved 17 April 2020 — https://api.fda.gov/drug/drugsfda.json?search=openfda.brand_name:%22TUKYSA%22
- NCI, Tucatinib — https://www.cancer.gov/about-cancer/treatment/drugs/tucatinib
- NCI, Targeted Therapy for Cancer — https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies
- NCI, Signs and Symptoms of Breast Cancer — https://www.cancer.gov/types/breast/symptoms
- SEER Cancer Stat Facts, Female Breast Cancer — https://seer.cancer.gov/statfacts/html/breast.html
How this article was prepared
An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.
The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.
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Put the story in context
Prevention, possible warning signs, screening, and diagnosis
This story relates to Breast cancer. The information below is general: it does not reveal anything else about a public person’s health, and not every point applies to every cancer. Personal advice depends on age, symptoms, family history, exposures, and medical history.
Prevention and risk reduction
Not every cancer can be prevented. Avoiding tobacco, protecting skin from ultraviolet radiation, limiting alcohol, staying active, and receiving recommended HPV or hepatitis B vaccination can lower the risk of certain cancers. A risk factor is not a prediction or a cause in one individual.
Symptoms and possible early signs
Possible signs vary and are often caused by conditions other than cancer. Changes worth discussing include a new lump, unexplained bleeding or weight loss, a persistent cough, lasting bowel or bladder changes, a changing skin spot, or symptoms that persist or worsen. Some early cancers cause no symptoms.
Screening and early detection
Screening looks for certain cancers before symptoms begin. Recommended tests exist only for some cancers and depend on age and risk. Screening can have benefits and harms; it is not the same as evaluating a new symptom, and there is no single routine scan or blood test that reliably screens for every cancer.
How cancer is diagnosed
Diagnosis may involve a history and exam, imaging, laboratory tests, and often a biopsy. Pathology can identify the cancer type and may test biomarkers that guide treatment. Symptoms, screening results, tumor markers, or online stories alone cannot confirm cancer.
Learn about this story’s cancer topic
A public story may encourage questions, but it should not be used to estimate your risk or choose testing. Contact a healthcare professional about a persistent or concerning change. Seek urgent care for severe or rapidly worsening symptoms.