Tucatinib

Overview of Tucatinib

Tucatinib is a highly selective, oral tyrosine kinase inhibitor (TKI) that targets the human epidermal growth factor receptor 2 (HER2) — a key driver in several aggressive cancers. By inhibiting HER2 signaling within cancer cells, tucatinib disrupts pathways that promote tumor growth and survival.

• Generic Name: Tucatinib
• Drug Class: HER2-selective Tyrosine Kinase Inhibitor
• Route of Administration: Oral
• Formulation: 50 mg and 150 mg tablets

Tucatinib is approved for use in combination therapy for HER2-positive metastatic breast cancer and HER2-positive, RAS wild-type metastatic colorectal cancer, particularly in patients who have progressed after prior anti-HER2 regimens. It is one of the few HER2-targeted therapies with proven clinical benefit in brain metastases, offering a meaningful survival advantage in this hard-to-treat population.

With its targeted mechanism, oral dosing convenience, and favorable tolerability profile, tucatinib represents a critical advancement in treating HER2-driven cancers.

Molecular Characteristics of Tucatinib

• 🧾 IUPAC Name:N-[4-[[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl]oxy]-3-methoxyphenyl]-6,6-dimethyl-5,6-dihydro-4H-pyran-2-carboxamide
• Molecular Formula:C₂₆H₂₉ClN₆O₃
• Molecular Weight:508.00 g/mol
• CAS Registry Number:937263-43-9
• Drug Class:
  Tyrosine Kinase Inhibitor (TKI)
  Highly selective for the HER2 receptor, with minimal activity on EGFR

Physical & Pharmaceutical Properties

• Formulation: Oral film-coated tablets
• Tablet Colors:
  • 50 mg: white to off-white, oval-shaped tablet
  • 150 mg: yellow, oval-shaped tablet
  • Both are debossed with identifying codes
• Solubility:
  • Soluble in dimethyl sulfoxide (DMSO) and slightly soluble in aqueous solutions
  • Poor water solubility — hence formulated with excipients for oral absorption
• Stability & Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C

Dosage & Administration

• Route of Administration: Oral (by mouth)
• Available Strengths:
  • 50 mg tablet
  • 150 mg tablet
  • Typically dosed as 150 mg twice daily (total 300 mg/day)

Mechanism of Action: How Tucatinib Inhibits HER2 Signaling

How Tucatinib Inhibits HER2

Tucatinib is a small-molecule tyrosine kinase inhibitor (TKI) that targets the intracellular kinase domain of the HER2 receptor (human epidermal growth factor receptor 2), a key driver of tumor growth in specific cancers.

Unlike non-selective TKIs inhibiting EGFR (HER1), tucatinib is highly selective for HER2, reducing off-target effects such as rash and diarrhea. Tucatinib binds reversibly and competitively to the ATP-binding site on HER2’s intracellular portion, preventing activation of downstream growth signals that promote cancer cell proliferation and survival.

Dual HER2 Blockade with Trastuzumab

While tucatinib works inside the cell, Trastuzumab — a monoclonal antibody — binds to the extracellular domain of HER2, preventing receptor dimerization and signaling from the cell surface.

When used together:

• Trastuzumab blocks HER2 activity from the outside, preventing receptor activation and antibody-dependent cell-mediated cytotoxicity (ADCC).
• Tucatinib blocks HER2 activity from the inside, inhibiting intracellular phosphorylation and signal transduction.

This dual HER2 blockade produces a synergistic anti-tumor effect, particularly in HER2-overexpressing tumors like certain breast and colorectal cancers.

Key Cellular Pathways Blocked

Once activated, HER2 triggers downstream pathways that support:

• Cell growth
• Survival
• Angiogenesis
• Resistance to apoptosis

Tucatinib blocks two central pro-survival signaling cascades:

PI3K/AKT/mTOR Pathway

• Regulates cell growth, glucose metabolism, and resistance to cell death
• HER2 signaling activates PI3K, which then activates AKT and mTOR
• Tucatinib disrupts this cascade, leading to apoptosis and reduced tumor growth

RAS/RAF/MEK/ERK (MAPK) Pathway

• Governs cell division and proliferation
• By inhibiting HER2, tucatinib downregulates MAPK signaling that leads to reduced tumor proliferation and increased sensitivity to other treatments

Indications & Uses of Tucatinib

Tucatinib, available as TUKYSA® and in the generic version Tucaxin, is an FDA-approved oral HER2-selective tyrosine kinase inhibitor used to treat HER2-positive cancers.

HER2-Positive Metastatic Breast Cancer

Approved Indication:

Tucatinib is used in combination with Trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Key Features:

• Targets patients with HER2 gene amplification or overexpression
• Effective in patients with active or stable brain metastases
• Improves progression-free survival (PFS) and overall survival (OS)
• Combines with standard agents to form a triple-therapy regimen

Approved Combination Therapy:

• Tucatinib: 150 mg twice daily (oral)
• Trastuzumab: IV or subcutaneous administration
• Capecitabine: Oral prodrug of 5-FU, taken within 30 minutes after a meal

Tucatinib’s ability to cross the blood-brain barrier makes it particularly effective for managing CNS disease, a common challenge in metastatic HER2-positive breast cancer.

HER2-Positive, RAS Wild-Type Metastatic Colorectal Cancer (mCRC)

Approved Indication:

Tucatinib is used in combination with Trastuzumab for the treatment of adult patients with RAS wild-type, HER2-positive metastatic colorectal cancer, whose disease has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Key Features:

• Targets HER2 overexpression in RAS wild-type tumors
• Offers a chemotherapy-free regimen
• Provides tumor shrinkage and durable responses in a previously untreatable subset

Approved Combination Therapy:

• Tucatinib: 150 mg twice daily (oral)
• Trastuzumab: Typically administered IV

Tucatinib+Trastuzumab+Capecitabine  marks the first HER2-directed regimen approved for mCRC — a significant advancement in personalized cancer treatment.

Summary of Therapy Combinations

Cancer Type	Tucatinib Used With	Indication
HER2+ Breast Cancer	Trastuzumab + Capecitabine	After ≥1 prior anti-HER2 regimen, including brain metastases
HER2+, RAS WT Colorectal CA	Trastuzumab	After prior chemo regimens (fluoropyrimidine, oxaliplatin, irinotecan)

Clinical Trials Supporting Tucatinib 

Tucatinib’s clinical effectiveness has been demonstrated in two pivotal, multicenter trials — HER2CLIMB and MOUNTAINEER — which evaluated its safety, efficacy, and survival benefits in heavily pretreated patients with HER2-positive cancers.

HER2CLIMB Trial Summary

Study Title: HER2CLIMB – A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial

Indication: HER2-positive metastatic breast cancer

Combination Studied: Tucatinib + Trastuzumab + Capecitabine

Population:

• 612 adult patients with HER2+ unresectable locally advanced or metastatic breast cancer
• All patients had received at least one prior HER2-directed therapy
• Notably, 48% had brain metastases at baseline

Key Outcomes:

• Progression-Free Survival (PFS):
  • 7.8 months in the tucatinib group vs 5.6 months in the placebo group
  • Hazard Ratio (HR): 0.54 → 46% reduction in risk of disease progression or death
• Overall Survival (OS):
  • 21.9 months vs 17.4 months
  • HR: 0.66 → 34% reduction in risk of death
• Objective Response Rate (ORR):
  • 40.6% with tucatinib vs 22.8% with placebo

Brain Metastases Subgroup:

• PFS (CNS subgroup):
  • 7.6 months vs 5.4 months
  • HR: 0.48 → 52% reduction in CNS progression or death
• Intracranial ORR:
  • 47.3% (tucatinib group)
  • 4.2% had a complete response

HER2CLIMB was the first randomized trial to include patients with active brain metastases — and showed significant benefit in this high-risk group.

MOUNTAINEER Trial Summary

Study Title: MOUNTAINEER – Phase 2, Open-Label, Multicenter Trial

Indication: HER2-positive, RAS wild-type metastatic colorectal cancer (mCRC)

Combination Studied: Tucatinib + Trastuzumab (no chemotherapy)

Population:

• 84 adult patients with HER2-positive, RAS wild-type mCRC
• All had progressed on standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan)

Key Outcomes:

• Objective Response Rate (ORR):
  • 38.1% (confirmed partial or complete response)
  • Complete Response: 3.6%
  • Partial Response: 35%
• Median Duration of Response (DoR):
  • 12.4 months
  • Some responses lasted over 2 years
• Disease Control Rate (DCR):
  • 71.4% (responses + stable disease)

MOUNTAINEER provided the basis for the first HER2-targeted treatment approval in colorectal cancer and represents a breakthrough in personalized medicine for mCRC.

Efficacy Summary Table

Trial	Indication	PFS	OS	ORR	Brain Met Response
HER2CLIMB	HER2+ Breast Cancer	7.8 mo vs 5.6	21.9 mo vs 17.4	40.6% vs 22.8%	52% ↓ CNS progression
MOUNTAINEER	HER2+, RAS WT mCRC	—	—	38.10%	Not applicable

Clinical Impact

• Tucatinib + Trastuzumab + capecitabine is now considered a standard regimen for HER2+ metastatic breast cancer, especially with brain involvement.
• Tucatinib + Trastuzumab provides a chemotherapy-free alternative for HER2+ colorectal cancer — offering efficacy with better tolerability.

 

Pharmacokinetics of Tucatinib

Tucatinib exhibits well-defined pharmacokinetic (PK) properties that support its efficacy, tolerability, and twice-daily oral dosing schedule. Below are the key parameters related to its absorption, metabolism, distribution, and elimination, along with how the drug behaves in systemic circulation.

Absorption & Tmax (Time to Peak Concentration)

After oral administration, tucatinib is moderately absorbed into the systemic circulation.

• Time to Peak (Tmax): Approximately 2 to 4 hours after oral dosing

• Food Effect:

  • Tucatinib may be taken with or without food

  • High-fat meals do not significantly impact overall exposure

• Bioavailability: Approximate absolute bioavailability is ~40%

This allows for flexible dosing schedules and convenient home administration.

Metabolism

Tucatinib undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes.

• Major Pathways:

  • CYP2C8 – Primary contributor

  • CYP3A4 – Secondary pathway

• Metabolites:

  • Tucatinib is metabolized to inactive metabolites

  • These are not believed to contribute to efficacy or toxicity

Drug-Drug Interaction Caution:

• Co-administration with strong CYP2C8 or CYP3A4 inhibitors or inducers may alter tucatinib plasma levels

• Avoid: St. John’s Wort, rifampin, and other strong CYP inducers

Plasma Protein Binding

• Tucatinib exhibits high plasma protein binding, estimated at ~97%

• This influences its distribution and helps maintain effective drug levels in systemic circulation

• Despite high protein binding, the free (active) concentration remains sufficient to inhibit HER2 kinase activity

Elimination

• Half-Life (t½): Approximately 8.5 hours
  → Supports twice-daily dosing

• Route of Excretion:

  • Feces (primary): ~86%

  • Urine (renal): ~4%

• Clearance:

  • Primarily non-renal

  • Driven largely by hepatic metabolism and biliary elimination

Plasma Concentration Curve (Typical PK Profile)

• Y-axis: Plasma concentration (ng/mL)

• X-axis: Time (hours)

Curve Details:

• Rapid rise to peak at ~3 hours

• Gradual decline following first-order kinetics

• Minimal accumulation at steady-state with BID dosing

• No significant food-related fluctuation

 

Parameter	Value
Bioavailability	~40%
Tmax	2–4 hours
Half-life (t½)	~8.5 hours
Protein Binding	~97%
Primary Metabolism	CYP2C8 (major), CYP3A4 (minor)
Excretion	~86% feces, ~4% urine

Here is the simulated plasma concentration-time curve for Tucatinib following oral administration. It illustrates:

• Tmax (~2–4 hours): the point where peak plasma concentration occurs
• Absorption Phase: rapid increase due to bioavailability and ka
• Elimination Phase: gradual decline as the drug is metabolized and excreted

Dosage & Administration of Tucatinib (TUKYSA®)

Tablet Strengths

Tucatinib is available in two oral film-coated tablet strengths, designed to support accurate dosing and flexible titration based on the treatment regimen:

• 50 mg tablet

  • Appearance: White to off-white, oval-shaped

  • Debossed with identifying code (e.g., “TUC 50”)

• 150 mg tablet

  • Appearance: Yellow, oval-shaped

  • Debossed with identifying code (e.g., “TUC 150”)

Tablets are packaged in bottles and should be stored at 20°C to 25°C (68°F to 77°F).

Recommended Dose & Schedule

• Standard Dose:

  • 150 mg orally, twice daily (every ~12 hours)

  • Total daily dose: 300 mg

• Administration Duration:

  • Administered continuously until disease progression or unacceptable toxicity

Dosing Time Guidance

• Take at consistent times each day (e.g., 8 AM and 8 PM)

• Maintain a ~12-hour interval between doses

How to Take Tucatinib

• With or Without Food:
  Tucatinib may be taken regardless of meals. Food does not significantly impact its absorption.

• Swallow Whole:

  • Take tablets whole with water

  • Do not crush, split, or chew

• Missed Dose Instructions:

  • If a dose is missed, skip it

  • Continue with the next scheduled dose

  • Do not double the dose to compensate

Treatment Duration

• Ongoing Therapy:

  • Continue until disease progression or development of intolerable side effects

• Dose Modification:

  • May pause or reduce dosage based on toxicity management protocols

  • Particularly for severe diarrhea or elevated liver enzymes

Combination Regimen Guidance

Tucatinib is not used as monotherapy — it is always prescribed as part of a combination regimen based on cancer type:

HER2-Positive Metastatic Breast Cancer

Triple Therapy Regimen:

• Tucatinib: 150 mg twice daily (oral)

• Trastuzumab: IV or subcutaneous injection (dose per label)

• Capecitabine: 1000 mg/m² orally, twice daily for 14 days, followed by a 7-day rest (21-day cycle)

  • Must be taken within 30 minutes after a meal

Patients must have received at least one prior anti-HER2 regimen in the metastatic setting.

HER2+, RAS Wild-Type Metastatic Colorectal Cancer

HER2+, RAS Wild-Type Metastatic Colorectal Cancer

Dual Therapy Regimen:

• Tucatinib: 150 mg twice daily (oral)

• Trastuzumab: IV infusion every 3 weeks (or as clinically indicated)

This chemotherapy-free regimen is the first HER2-targeted treatment approved in this indication.

Parameter	Detail
Available Strengths	50 mg and 150 mg tablets
Recommended Dose	150 mg twice daily (300 mg/day)
Administration	Oral, with or without food
Tablet Instructions	Swallow whole, do not crush/split
Duration	Until progression or toxicity
Combinations	Trastuzumab ± Capecitabine

 

Safety Profile of Tucatinib 

Tucatinib, a selective HER2-directed tyrosine kinase inhibitor, has a generally manageable safety profile, especially when used in combination with Trastuzumab and capecitabine. However, it may cause certain adverse events that require dose modification, temporary interruption, or discontinuation.

Common Adverse Reactions

(Based on pooled safety data from the HER2CLIMB trial)

The most common side effects (all grades) reported in patients receiving tucatinib + Trastuzumab + capecitabine include:

Risk Area	Monitoring / Guidance	Grade ≥3
Hepatotoxicity	LFTs every 3 weeks; interrupt or reduce dose if Grade ≥3 elevations	12%
Diarrhea	Early intervention with antidiarrheals; hydrate; adjust dose if needed	13%
Pregnancy	Avoid use; use contraception; risk of fetal harm	2%
Lactation	Discontinue breastfeeding during and for 1 week after last dose	4%
Liver Impairment	Use caution in severe hepatic dysfunction; monitor LFTs closely	2%
Drug Interactions	Avoid strong CYP2C8/CYP3A4 inhibitors or inducers	6% (ALT), 4% (AST)
Stomatitis (mouth sores)	27%	1%
Decreased appetite	23%	<1%
Headache	22%	<1%
Anemia	19%	4%

Most side effects are reversible with supportive care or dose adjustment.

Serious Risks and Warnings

Tucatinib carries several clinically significant risks that require proactive monitoring:

Hepatotoxicity

• Elevations in ALT, AST, and bilirubin have been reported.
• Can be severe or life-threatening in rare cases.
• Monitoring recommendation:
  • LFTs prior to starting therapy and every 3 weeks during treatment.
• Management:
  • Dose reduction, interruption, or discontinuation based on severity.

Severe Diarrhea

• Can result in dehydration, hypotension, renal dysfunction.
• Usually occurs within the first month of treatment.
• Management:
  • Early use of antidiarrheals (e.g., loperamide)
  • Oral fluid intake and electrolyte management

Fetal Harm (Embryo-Fetal Toxicity)

• Tucatinib can cause fetal harm when administered to a pregnant woman.
• Mechanism: HER2 is involved in fetal development (especially cardiac tissue).
• Contraception guidance:
  • Females of reproductive potential must use effective contraception during treatment and for at least 1 week after the final dose.

Pregnancy

• Contraindicated unless no alternatives exist and the potential benefit outweighs the risk.
• Preclinical animal studies showed embryotoxicity and fetal malformations.
• Pregnancy testing is recommended before initiation of therapy.

Lactation

• It is unknown if tucatinib is excreted in human milk.
• Due to the potential for serious adverse reactions in infants:
  • Breastfeeding is not recommended during treatment and for at least 1 week after the last dose.

Hepatic Impairment

• The liver metabolizes Tucatinib.
• No dose adjustment is required for mild to moderate liver impairment.
• Caution is advised in patients with severe hepatic impairment, although specific dosing recommendations have not been established due to limited data.

Renal Impairment

• No clinically meaningful differences in pharmacokinetics were observed in patients with mild to moderate renal impairment.
• Data are limited for severe renal impairment (eGFR <30 mL/min).

Key Safety Recommendations

Risk Area	Monitoring / Guidance
Hepatotoxicity	LFTs every 3 weeks; interrupt or reduce dose if Grade ≥3 elevations
Diarrhea	Early intervention with antidiarrheals; hydrate; adjust dose if needed
Pregnancy	Avoid use; use contraception; risk of fetal harm
Lactation	Discontinue breastfeeding during and for 1 week after last dose
Liver Impairment	Use caution in severe hepatic dysfunction; monitor LFTs closely
Drug Interactions	Avoid strong CYP2C8/CYP3A4 inhibitors or inducers

 

Prescribing Considerations and Risk Management for Tucatinib

Boxed Warnings

Tucatinib does not currently carry an FDA boxed warning (also known as a black box warning).

However, it includes serious precautions related to hepatotoxicity, embryo-fetal toxicity, and severe diarrhea, which must be carefully monitored.

Liver Function Monitoring

Rationale:

Tucatinib is primarily metabolized in the liver and has been associated with transient or severe elevations in liver enzymes (ALT, AST, bilirubin). Cases of hepatotoxicity have led to dose modification or treatment discontinuation in clinical trials.

Monitoring Guidelines:

• Perform baseline liver function tests (LFTs) before starting therapy.

• Monitor ALT, AST, and total bilirubin every 3 weeks during treatment.

• Increase monitoring frequency if elevated liver enzymes are detected.

Management:

• Grade 1–2 (mild/moderate): Continue with close monitoring.

• Grade 3 (severe): Interrupt treatment and resume at a reduced dose once resolved.

• Grade 4 or persistent Grade ≥3: Discontinue tucatinib permanently.

Co-administration with hepatotoxic agents may increase the risk.

Drug–Drug Interactions (DDIs)

Metabolic Pathways:

Tucatinib is metabolized primarily by CYP2C8 and to a lesser extent by CYP3A4.

Avoid Co-Administration With:

Type	Examples	Effect
CYP3A/2C8 inducers	Rifampin, carbamazepine, St. John’s Wort	Decrease tucatinib levels → reduced efficacy
CYP3A/2C8 inhibitors	Ketoconazole, gemfibrozil, clarithromycin	Increase tucatinib exposure → increased toxicity risk

Recommendations:

• Avoid strong inhibitors/inducers.

• Monitor for toxicity if moderate inhibitors are required.

• Review all patient medications (including herbal supplements) for interaction risk.

 

Contraceptive Use & Pregnancy Prevention

Embryo-Fetal Toxicity Risk:

Tucatinib can cause fetal harm based on mechanism of action and animal data.
HER2 plays a role in fetal cardiac and neural development.

Contraceptive Guidance:

• Females of reproductive potential must use effective contraception during treatment and for at least 1 week after the last dose.

• Pregnancy testing is recommended prior to initiating therapy.

• Male patients with partners of childbearing potential should also use effective contraception during treatment and for 1 week after the final dose.

Counsel patients on contraceptive options and the importance of adherence.

Prescriber Takeaway

Risk Area	Prescribing Action
Hepatotoxicity	LFTs q3w; reduce or stop for Grade ≥3 elevations
CYP-mediated Interactions	Avoid strong CYP2C8/CYP3A4 modulators
Pregnancy/Fertility	Contraception required; test before starting
Severe Adverse Reactions	Discontinue if toxicity persists or becomes life-threatening
Breastfeeding	Avoid during treatment and for ≥1 week after stopping

Blood–Brain Barrier (BBB) Activity of Tucatinib

The Challenge of Brain Metastases in HER2-Positive Cancers

In HER2-positive metastatic breast cancer, brain metastases occur in up to 50% of patients. The blood–brain barrier (BBB) limits the entry of many anti-cancer drugs into the CNS.

Traditional HER2-targeted therapies like Trastuzumab have limited BBB penetration, leading to poor outcomes in patients with brain metastases.

Tucatinib’s CNS Penetration: A Key Innovation

Tucatinib, a small-molecule HER2-selective TKI, can penetrate the BBB and treat HER2-positive tumors within the CNS.

Key Pharmacologic Features:

• Small size and lipophilic structure enhance BBB permeability

• Selective HER2 targeting reduces systemic toxicity

• Demonstrated CNS tumor reduction and delay in progression in clinical trials

Tucatinib reaches therapeutic concentrations in brain tissue, directly acting on intracranial lesions.

Clinical Evidence of CNS Activity

HER2CLIMB Trial CNS Subgroup Analysis:

• 48% of enrolled patients had brain metastases (active or stable)

• 52% reduction in risk of CNS progression or death (HR = 0.48; 95% CI: 0.34–0.69)

Intracranial Outcomes:

• Median PFS: 7.6 months (Tucatinib) vs 5.4 months (control)

• Intracranial ORR: 47.3% (Tucatinib group)

• Clinical Benefit Rate (CBR): 70.1%

CNS-Specific Benefits:

• Delayed need for whole-brain radiation therapy (WBRT)

• Controlled CNS progression

• Prolonged survival in patients with active brain metastases

Tucatinib is the first and only HER2-targeted therapy with Phase 2 randomized trial evidence of CNS-specific efficacy.

Unique Benefit Over Similar Agents

Feature	Tucatinib	Lapatinib	Neratinib	Trastuzumab
BBB Penetration	High	Moderate	Moderate	Very limited
Selectivity for HER2 vs EGFR	High (HER2 only)	Low (HER2 & EGFR)	Low (HER2 & EGFR)	HER2 only
CNS Response (Clinical Trials)	Proven in HER2CLIMB	Limited	Observed in ExteNET	Minimal
Tolerability Profile	Favorable	Higher GI toxicity	Higher GI/liver tox	Well-tolerated

Tucatinib’s high selectivity for HER2 and limited EGFR inhibition translate to fewer side effects (e.g., less diarrhea and rash), making it better tolerated and suitable for longer CNS-directed therapy.

Regulatory Approvals

U.S. Food and Drug Administration (FDA)

Initial Approval:

• Date: April 17, 2020

• Indication: Tucatinib + Trastuzumab + Capecitabine for HER2-positive metastatic breast cancer, including brain metastases, after prior anti-HER2 regimens.

Expanded Approval:

• Date: January 19, 2023

• Indication: Tucatinib + Trastuzumab for RAS wild-type, HER2-positive mCRC, after prior chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan).

International Regulatory Approvals

European Medicines Agency (EMA)

• Authorization Date: February 2021

• Indication: HER2-positive metastatic breast cancer

• Approval Type: Centralized across EU countries

Health Canada

• Approval Date: August 2020

• Indication: HER2-positive metastatic breast cancer after anti-HER2 therapy

Therapeutic Goods Administration (TGA – Australia)

• Indication: HER2+ breast cancer with CNS disease

• Access: Distributed via national oncology programs

Food and Drug Administration – Philippines

• Tucatinib (TUKYSA®) is approved for use in HER2-positive breast cancer

• Expansion to colorectal indication pending or under review (based on region)

Global approvals are based primarily on HER2CLIMB and MOUNTAINEER clinical trial results.

Regulatory Summary Table

Agency	Indication Approved	Approval Year
FDA (US)	HER2+ breast cancer; HER2+, RAS WT mCRC	2020, 2023
EMA (EU)	HER2+ metastatic breast cancer	2021
Health Canada	HER2+ metastatic breast cancer	2020
TGA (AUS)	HER2+ metastatic breast cancer (CNS disease)	2021
FDA-PH (Philippines)	HER2+ metastatic breast cancer	Approved

Downloads & Resources

• Prescribing info (PDF)
• Patient brochure
• MOA animation video
• Clinical trial data sheet
• HCP prescribing toolkit