What Is Tucatinib (Tukysa)? FDA Approval, Turkish Marketing Authorization, and Reimbursement Status
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What Is Tukysa (Tucatinib)?
The active ingredient tucatinib of Tukysa, developed to prevent uncontrolled cell proliferation in advanced or metastatic HER2-positive cancers, is an orally administered targeted smart cancer drug. As a small-molecule tyrosine kinase inhibitor (TKI) Tukysa is a treatment option that demonstrated intracranial activity in a randomized phase III study including patients with brain metastases.[2]
Tukysa Price Information
As of October 2026 Tukysa's pharmacy retail prices in Türkiye are as follows:
- Tukysa 150 mg 84 Film-Coated Tablets: TRY 148,266.67
- Tukysa 50 mg 88 Film-Coated Tablets: TRY 51,872.07
Prescription type: Restricted white prescription.
*Drug prices may change periodically depending on Ministry of Health pricing decrees and euro-value updates.
Drug Identification and Official Indications
- First Turkish Marketing Authorization Date: 24 December 2025
- First FDA Approval Date: 17 April 2020[1]
- European Union (EMA) Approval Date: 11 February 2021[5]
- Developer / Marketing Authorization Holder: Developed by Seagen Inc.; Seagen became part of Pfizer in 2023. In Türkiye, it is marketed by Pfizer PFE İlaçları A.Ş.
- Class / Category: Antineoplastic agent, small-molecule tyrosine kinase inhibitor (TKI)
- FDA-Approved Indications (U.S.):[1]
- HER2-Positive Advanced / Metastatic Breast Cancer: Previously at least one anti-HER2-based treatment in the metastatic setting; used in combination with trastuzumab and capecitabine in adult patients with or without brain metastases trastuzumab and capecitabine are used in combination.
- HER2-Positive Metastatic Colorectal Cancer (accelerated approval): In unresectable or metastatic colorectal cancer that has progressed after fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, RAS wild-type and HER2-positive, used in combination with trastuzumab .
- European Union (EMA) Indication: Breast cancer only. In HER2-positive locally advanced or metastatic breast cancer, used in combination with trastuzumab and capecitabine in adult patients who have previously received at least two anti-HER2 treatment regimens. Colorectal cancer is not an approved indication in the EU.[5]
What Is Its Mechanism of Action?
Tucatinib selectively targets the tyrosine kinase domain in the intracellular portion of the HER2 (human epidermal growth factor receptor 2) protein on the surface of tumor cells. By binding to this region, it inhibits receptor phosphorylation (activation) and downstream growth signals.
Features distinguishing Tukysa from other HER2 TKIs:
- High selectivity for HER2: Tucatinib targets HER2 without significantly suppressing EGFR (HER1). Because of this selectivity, EGFR-related rash and diarrhea, frequently seen with TKIs that also inhibit EGFR, such as lapatinib and neratinib, are expected to be less prominent. However, no randomized study has directly compared these drugs. Diarrhea is also a common adverse effect with tucatinib combination therapy (see below).
- Central nervous system activity: In patients with brain metastases in the HER2CLIMB study, it significantly reduced the risks of intracranial progression and death.[3]
📜 Approval Timeline and Milestones
- June 2017: The FDA granted tucatinib Orphan Drug status for the treatment of breast cancer that had metastasized to the brain.
- 2017 (third quarter): Orphan Drug status was also granted for the treatment of HER2-positive colorectal cancer.
- December 2019: Results of the pivotal HER2CLIMB study were published in theNew England Journal of Medicine.[2]
- 17 April 2020: Based on HER2CLIMB data, the FDA approved the combination with trastuzumab and capecitabine for HER2-positive advanced or metastatic breast cancer.[1]
- 11 February 2021: The European Commission granted marketing authorization for the breast cancer indication.[5]
- 19 January 2023: Based on the MOUNTAINEER study, accelerated FDA approval was granted for use with trastuzumab in previously treated RAS wild-type, HER2-positive metastatic colorectal cancer. Making the approval permanent depends on the results of the ongoing phase III MOUNTAINEER-03 study. FDA approval was granted. The approval becoming permanent depends on the results of the ongoing phase III MOUNTAINEER-03 trial.[1][7]
- December 2025: Results of the phase III HER2CLIMB-05 study evaluating first-line maintenance therapy were presented at the San Antonio Breast Cancer Symposium.[6]
- 24 December 2025: Marketing authorization was granted in Türkiye.
🔍 Clinical Significance and New Developments
HER2CLIMB (pivotal phase III study): In 612 patients previously treated with trastuzumab, pertuzumab, and T-DM1, adding tucatinib increased median progression-free survival from 5.6 to 7.8 months (HR 0.54) and median overall survival from 17.4 to 21.9 months (HR 0.66), compared with trastuzumab and capecitabine therapy.[2]
Patients with brain metastases: A substantial proportion of patients with HER2-positive metastatic breast cancer develop brain metastases during the course of the disease. In patients with brain metastases in HER2CLIMB, the tucatinib combination:[3]
- Reduced the risk of intracranial progression or death by 68% (HR 0.32),
- Reduced the risk of death by 42% (HR 0.58; median overall survival 18.1 versus 12.0 months),
- Increased the intracranial response rate from 20.0% to 47.3% in patients with measurable brain lesions.
HER2CLIMB-05 (first-line maintenance, phase III): In 654 patients whose disease had not progressed after induction therapy, adding tucatinib to trastuzumab and pertuzumab maintenance therapy extended median progression-free survival from 16.3 to 24.9 months (HR 0.641; p<0.0001). Overall survival data are not yet mature.[6]
Note: HER2CLIMB-05 is clinical study data. First-line maintenance use is not among the approved indications listed above.
The infographic below shows Tukysa's mechanism of action and its effects on intracellular signaling pathways:
Turkish Marketing Authorization and SSI Reimbursement Status
Marketing Authorization Status: Tukysa (tucatinib) on 24 December 2025 was granted marketing authorization by the Turkish Medicines and Medical Devices Agency (TİTCK). It can therefore be supplied through pharmacies in Türkiye without the need for obtaining the drug from abroad.
SSI Reimbursement: TİTCK marketing authorization and SSI reimbursement are independent processes. The granting of marketing authorization for a drug does not mean that it will automatically be reimbursed by SSI. Reimbursement coverage and conditions are determined according to the Health Implementation Communiqué (SUT) and SSI's reimbursement list.
Dosage Interval and Method of Administration
Tukysa is available as orally administered film-coated tablets. Unless otherwise specified by the physician, treatment is administered according to the following rules:[1][5]
- Standard dose: 300 mg twice daily (two 150 mg tablets in the morning and two in the evening), for a total of 600 mg/day.
- Dose-reduction steps: Because of adverse effects, the dose may be reduced successively to 250 mg, 200 mg, and 150 mg twice daily. 50 mg tablets are used for intermediate doses.
- Method of administration: It may be taken at the same times every day, approximately 12 hours apart, with or without food .
- Tablets must not be crushed, chewed, or split; they must be swallowed whole.
- Missed or vomited dose: An additional or replacement dose should not be taken. Treatment should continue by taking the next dose at the scheduled time.
How Does Resistance to Tukysa Develop?
In targeted therapies, tumor cells may develop mechanisms over time that overcome the effect of the drug. The mechanisms below have been identified largely in laboratory (preclinical) studies of resistance to HER2-targeted therapies. Clinical data on tucatinib-specific resistance are still limited.
- Alternative pathway activation: Even when HER2 is suppressed, the cell may activate parallel signaling pathways such as PI3K/AKT/mTOR or MAPK/ERK .
- New mutations in the HER2 gene: Point mutations arising in the HER2 kinase domain may weaken the drug's binding to the receptor.
- Signaling through other HER family receptors: With increased expression of HER3 or EGFR (HER1), the growth signal may continue through alternative receptor pairings.
Drug Interactions and Monitoring Parameters
- CYP2C8 interactions (critical): Tucatinib is metabolized predominantly in the liver by the CYP2C8 enzyme. Strong CYP2C8 inhibitors (for example, the cholesterol medication gemfibrozil) increase tucatinib blood levels, thereby increasing the risk of toxicity, and should not be used concomitantly. Strong CYP3A or moderate CYP2C8 inducers (for example, rifampin) reduce the drug's blood levels and efficacy.[5]
- Effect of tucatinib on other drugs: Tucatinib is a strong CYP3A inhibitor. It may increase the blood levels of drugs metabolized by CYP3A that have a narrow therapeutic range (for example, midazolam). It may also increase the levels of P-glycoprotein substrates (for example, digoxin). Dose adjustment and close monitoring are required when used concomitantly with these drugs.[5]
- Monitoring for hepatotoxicity: ALT, AST, and total bilirubin levels should be monitored at the start of treatment and then every three weeks (or as clinically indicated). Depending on increases in these values, treatment may be interrupted, the dose may be reduced, or treatment may be discontinued.[5]
- Increase in serum creatinine: Tucatinib may increase serum creatinine levels (on average, by approximately 30%) by inhibiting the renal tubular excretion of creatinine without impairing kidney function. Therefore, other indicators should also be considered when assessing kidney function.[1][5]
- Pregnancy and contraception: In animal studies, it caused embryo-fetal death and malformations. Female patients of reproductive potential and male patients with partners of reproductive potential should use an effective method of contraception during treatment and for at least 1 week after the last dose.[5]
Most Common Adverse Effects and Toxicity Profile
The main adverse effects observed in patients receiving the combination of tucatinib, trastuzumab, and capecitabine in the HER2CLIMB study are listed below. The rates in the comparison arm receiving placebo, trastuzumab, and capecitabine are given in parentheses.[1]
- Diarrhea: 81% (53%); grade 3: 12%
- Hand-foot syndrome: 63% (53%)
- Nausea: 58% (44%)
- Hepatotoxicity: 42% (24%)
- Vomiting: 36% (25%)
- Oral sores (stomatitis): 32% (21%)
- Decreased appetite: 25% (20%)
- Anemia: 21% (13%)
- Rash: 20% (15%)
- Increase in serum creatinine: 14% (1.5%)
An increase in ALT was observed in 46% of patients (grade ≥3: 8%), and an increase in AST was observed in 43% (grade ≥3: 6%) in laboratory values.[1] A substantial proportion of hand-foot syndrome is attributable to capecitabine in the combination; its occurrence at a rate of 53% in the placebo arm also demonstrates this.
When used with trastuzumab in colorectal cancer (MOUNTAINEER), the most common adverse effects were diarrhea (64%), fatigue (44%), rash (37%), and nausea (35%).[1] In the final analysis of MOUNTAINEER, the confirmed objective response rate was reported as 39.3%, the median duration of response as 15.2 months, and median overall survival as 23.9 months.[4]
Important Physician's Note: In patients who develop capecitabine-related hand-foot syndrome or tucatinib-related diarrhea, supportive treatment should be initiated early, before symptoms reach grade 3–4, and dose reduction should be planned by the oncology physician if necessary.
References
- TUKYSA (tucatinib) Prescribing Information (U.S.). Pfizer/Seagen. Adverse Reactions, Dosage and Administration sections.
- Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597–609. doi:10.1056/NEJMoa1914609
- Lin NU, Borges V, Anders C, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38(23):2610–2619. doi:10.1200/JCO.20.00775
- Strickler JH, et al. MOUNTAINEER final analysis: tucatinib plus trastuzumab in HER2-positive, RAS wild-type metastatic colorectal cancer. Nature Communications. 2026.
- European Medicines Agency (EMA). Tukysa – EPAR and Summary of Product Characteristics (SmPC). Pfizer Europe MA EEIG.
- HER2CLIMB-05: A phase III study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer. J Clin Oncol. Published online December 10, 2025 (2025 San Antonio Breast Cancer Symposium).
- ClinicalTrials.gov. MOUNTAINEER-03: Comparison of tucatinib, trastuzumab, and mFOLFOX6 with standard treatment in first-line HER2+ metastatic colorectal cancer. NCT05253651.
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