Alunbrig: Uses, Dosage & Side Effects

A next-generation ALK tyrosine kinase inhibitor for the treatment of adults with advanced ALK-positive non-small cell lung cancer (NSCLC)

Rx ATC: L01ED04 ALK Inhibitor
Active Ingredient
Brigatinib
Available Forms
Film-coated tablets
Strengths
30 mg, 90 mg, 180 mg
Manufacturer
Takeda

Alunbrig (brigatinib) is a targeted anticancer medicine belonging to the class of tyrosine kinase inhibitors. It is used to treat adults with advanced non-small cell lung cancer (NSCLC) driven by an abnormal form of the anaplastic lymphoma kinase (ALK) gene. Brigatinib works by blocking the ALK protein that stimulates cancer cell growth and division. It is taken orally as a once-daily tablet and is effective both as a first-line treatment for ALK-positive NSCLC and in patients whose disease has progressed on the first-generation ALK inhibitor crizotinib. Alunbrig demonstrates potent activity against many ALK resistance mutations and has notable efficacy against brain metastases, a common complication of ALK-positive lung cancer.

Quick Facts: Alunbrig

Active Ingredient
Brigatinib
Drug Class
ALK Inhibitor (TKI)
ATC Code
L01ED04
Common Uses
ALK+ NSCLC
Available Forms
Oral Tablet
Prescription Status
Rx Only

Key Takeaways

  • Alunbrig (brigatinib) is a next-generation ALK inhibitor taken once daily as an oral tablet for the treatment of advanced ALK-positive non-small cell lung cancer in adults.
  • Treatment starts at 90 mg daily for the first 7 days, then increases to 180 mg daily; this step-up schedule reduces the risk of early-onset pulmonary events that can occur during the first week.
  • Brigatinib has demonstrated superior progression-free survival compared to crizotinib in the landmark ALTA-1L trial, with particularly strong efficacy against brain metastases.
  • Common side effects include high blood pressure, elevated creatine phosphokinase, visual disturbances, elevated liver and pancreatic enzymes, hyperglycemia, diarrhea, and nausea; pulmonary events require immediate medical attention.
  • Grapefruit products must be avoided during treatment, and women of childbearing potential must use effective non-hormonal contraception during treatment and for 4 months after the last dose.

What Is Alunbrig and What Is It Used For?

Quick Answer: Alunbrig (brigatinib) is a targeted cancer medicine used to treat adults with advanced non-small cell lung cancer (NSCLC) caused by an abnormal ALK gene. It works by blocking the ALK protein that drives cancer cell growth, and is taken as a once-daily oral tablet.

Alunbrig contains the active substance brigatinib, which belongs to a class of anticancer medicines known as tyrosine kinase inhibitors. Specifically, brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor. It is used for the treatment of adults with advanced (locally advanced or metastatic) non-small cell lung cancer, the most common form of lung cancer, when the cancer is driven by a specific genetic alteration involving the ALK gene.

In approximately 3–5% of patients with non-small cell lung cancer, a chromosomal rearrangement creates an abnormal fusion of the ALK gene with another gene (most commonly EML4). This fusion produces an abnormal ALK protein – a kinase – that is continuously active and sends growth signals to cancer cells, driving their uncontrolled proliferation and survival. Cancers harboring this ALK rearrangement are referred to as ALK-positive NSCLC. ALK-positive lung cancer is more commonly found in younger patients, non-smokers or light smokers, and patients with adenocarcinoma histology.

Brigatinib blocks the activity of this abnormal ALK protein with high potency, thereby interrupting the signaling pathways that promote cancer cell growth and survival. By inhibiting ALK, brigatinib slows the growth and spread of ALK-positive lung cancer. Importantly, brigatinib is a next-generation (second-generation) ALK inhibitor, meaning it was specifically designed to overcome many of the resistance mutations that develop during treatment with first-generation ALK inhibitors such as crizotinib. Brigatinib demonstrates activity against a broad spectrum of ALK resistance mutations, including the particularly challenging G1202R mutation, which is one of the most common mechanisms of acquired resistance to earlier ALK inhibitors.

In addition to its potent ALK inhibitory activity, brigatinib also has activity against several other kinase targets including ROS1, IGF-1R (insulin-like growth factor 1 receptor), and FLT3. However, its primary clinical use is in ALK-positive NSCLC.

Alunbrig is approved by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and regulatory authorities in numerous other countries for the following indications:

  • First-line treatment of ALK-positive advanced NSCLC: Alunbrig can be used as a first-line (initial) treatment for adults with ALK-positive advanced non-small cell lung cancer who have not previously received an ALK inhibitor. The pivotal ALTA-1L trial demonstrated that brigatinib provided significantly superior progression-free survival compared to crizotinib, including superior intracranial (brain) responses.
  • Treatment after prior crizotinib therapy: Alunbrig is also approved for adults with ALK-positive advanced NSCLC who have previously been treated with crizotinib and whose disease has progressed. In this setting, brigatinib offers an effective treatment option for patients whose cancer has become resistant to first-generation ALK inhibition.

One of the distinguishing features of Alunbrig is its notable efficacy in the central nervous system (CNS). Brain metastases are a frequent complication of ALK-positive lung cancer, occurring in up to 30–40% of patients at diagnosis and in a substantial proportion during the course of the disease. Brigatinib has demonstrated significant intracranial activity, with high intracranial response rates and durable intracranial disease control in clinical trials, making it a particularly valuable treatment option for patients with brain metastases.

Understanding ALK-Positive Lung Cancer

ALK-positive NSCLC is identified through molecular testing of the tumor tissue or through liquid biopsy (blood test). Testing for ALK rearrangements is now standard practice in the diagnostic workup of non-small cell lung cancer, as it determines eligibility for targeted ALK inhibitor therapy. If you have been diagnosed with NSCLC, ask your doctor whether your tumor has been tested for ALK rearrangements and other actionable genetic alterations.

What Should You Know Before Taking Alunbrig?

Quick Answer: Do not take Alunbrig if you are allergic to brigatinib. Inform your doctor about any lung problems, high blood pressure, heart conditions, visual disturbances, muscle problems, pancreatic or liver disorders, kidney problems, or if you are pregnant or breastfeeding. Avoid grapefruit products and limit sun exposure during treatment.

Contraindications

There is one absolute contraindication to the use of Alunbrig:

  • Hypersensitivity: Do not take Alunbrig if you are allergic to brigatinib or any of the other ingredients in the tablet (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate type A, colloidal anhydrous silica, magnesium stearate, talc, macrogol, polyvinyl alcohol, or titanium dioxide).

Warnings and Precautions

Talk to your doctor before taking Alunbrig or during treatment if you have any of the following conditions or concerns:

  • High blood pressure (hypertension): Alunbrig can cause or worsen high blood pressure. Your doctor will monitor your blood pressure regularly and may prescribe or adjust antihypertensive medications as needed. Tell your doctor if you experience headache, dizziness, blurred vision, chest pain, or shortness of breath.
  • Slow heartbeat (bradycardia): Brigatinib may slow your heart rate. Inform your doctor if you experience chest discomfort, changes in your heartbeat, dizziness, lightheadedness, or fainting. Your doctor may adjust the dose of Alunbrig or of any concomitant medications that can also slow heart rate.
  • Visual disturbances: Report any visual changes during treatment, including flashes of light, blurred vision, or sensitivity to light. Your doctor may pause treatment and refer you to an ophthalmologist (eye specialist) for evaluation.
  • Muscle problems: Elevated creatine phosphokinase (CPK) is common with brigatinib and may indicate muscle damage. Report any unexplained muscle pain, tenderness, or weakness to your doctor. Blood tests will be performed regularly to monitor CPK levels.
  • Pancreatic problems: Elevated pancreatic enzymes (amylase and lipase) may indicate inflammation of the pancreas (pancreatitis). Tell your doctor if you develop pain in the upper abdomen, abdominal pain that worsens after eating and may radiate to the back, weight loss, or nausea.
  • Liver problems: Elevated liver enzymes (AST, ALT) may indicate liver cell damage. Tell your doctor if you develop pain on the right side of your abdomen, yellowing of the skin or eyes (jaundice), or dark urine.
  • High blood sugar (hyperglycemia): Brigatinib can cause elevated blood sugar levels. Tell your doctor if you feel very thirsty, need to urinate more frequently, feel very hungry, nauseous, weak, tired, or confused.
  • Sun sensitivity (photosensitivity): Limit your time in the sun during treatment and for at least 5 days after the last dose. Wear a hat, protective clothing, and apply sunscreen with both UVA and UVB protection and lip balm with an SPF of at least 30.
  • Kidney problems: If you have kidney problems or are receiving dialysis, inform your doctor. Symptoms of kidney issues may include nausea, changes in the amount or frequency of urination, and abnormal blood test results.

Your doctor may need to adjust the dose, temporarily interrupt treatment, or permanently discontinue Alunbrig depending on the severity of these effects. Regular blood tests and clinical assessments will be performed throughout treatment to monitor for potential complications.

Children and Adolescents

Alunbrig has not been studied in children and adolescents. Treatment with Alunbrig is not recommended for individuals under 18 years of age. The safety and efficacy of brigatinib in this population have not been established.

Pregnancy and Breastfeeding

Alunbrig is not recommended during pregnancy unless the benefit clearly outweighs the risk to the unborn child. Based on its mechanism of action and preclinical data, brigatinib has the potential to cause harm to a developing fetus. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking Alunbrig.

Women of childbearing potential treated with Alunbrig must use an effective non-hormonal method of contraception during treatment and for at least 4 months after the last dose. Non-hormonal contraception is specifically required because it is not known whether brigatinib may reduce the effectiveness of hormonal contraceptives. Ask your doctor about suitable contraceptive methods.

You should not breastfeed during treatment with Alunbrig. It is not known whether brigatinib passes into breast milk and could potentially harm the breastfed infant.

Men treated with Alunbrig should not father children during treatment and must use effective contraception during treatment and for at least 3 months after the last dose.

Driving and Operating Machinery

Alunbrig may cause visual disturbances, dizziness, and fatigue. If you experience these symptoms, do not drive or operate machinery until the symptoms resolve. Discuss with your doctor if you have concerns about your ability to perform these activities safely during treatment.

Important Information About Ingredients

Alunbrig contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Alunbrig contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is essentially sodium-free.

How Does Alunbrig Interact with Other Drugs?

Quick Answer: Alunbrig interacts with strong CYP3A4 inhibitors (e.g., ketoconazole) which increase brigatinib levels, and strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, St. John’s wort) which decrease its effectiveness. Grapefruit products must be avoided. Brigatinib may also increase levels of certain other medications including digoxin and cyclosporine.

Brigatinib is primarily metabolized by the CYP2C8 and CYP3A4 enzyme systems. Medications that inhibit or induce these enzymes can alter brigatinib levels in the body, potentially affecting both efficacy and toxicity. Additionally, brigatinib may affect the levels of other medications you take by inhibiting certain drug transporters. It is essential to inform your doctor about all medications, herbal products, and supplements you are taking before starting and during treatment with Alunbrig.

Major Interactions

Major Drug Interactions with Alunbrig
Interacting Drug Effect Clinical Significance
Ketoconazole, itraconazole, voriconazole (strong CYP3A4 inhibitors) Increased brigatinib plasma levels, greater risk of toxicity Avoid if possible; if unavoidable, reduce Alunbrig dose by approximately 50%
Rifampicin, rifabutin (strong CYP3A4 inducers) Significantly decreased brigatinib plasma levels, reduced efficacy Avoid combination; cancer treatment may be less effective
Carbamazepine, phenytoin, phenobarbital (antiepileptics / CYP3A4 inducers) Decreased brigatinib levels, potentially reduced anticancer activity Avoid combination; discuss alternative antiepileptic options with your doctor
St. John’s wort (herbal CYP3A4 inducer) Decreased brigatinib levels Do not use St. John’s wort during treatment with Alunbrig
Grapefruit and grapefruit juice Increased brigatinib levels due to CYP3A4 inhibition Avoid all grapefruit products during treatment

Other Notable Interactions

Other Drug Interactions with Alunbrig
Interacting Drug Effect Clinical Significance
Digoxin (P-gp substrate) Brigatinib may increase digoxin levels by inhibiting P-glycoprotein transport Monitor digoxin levels closely; dose adjustment may be needed
Dabigatran (P-gp substrate) Brigatinib may increase dabigatran levels Monitor for signs of bleeding; consider alternative anticoagulant
Cyclosporine, sirolimus, tacrolimus (immunosuppressants) Brigatinib may increase levels of these immunosuppressants Monitor drug levels and adjust doses accordingly
Methotrexate, sulfasalazine (BCRP substrates) Brigatinib may increase levels of these drugs Monitor for increased toxicity
Pravastatin, rosuvastatin (OATP substrates) Brigatinib may increase statin levels Monitor for muscle symptoms (myalgia, rhabdomyolysis)
Indinavir, nelfinavir, ritonavir, saquinavir (HIV protease inhibitors) Increased brigatinib levels (CYP3A4 inhibition) Use with caution; dose reduction of Alunbrig may be needed
Clarithromycin, telithromycin (macrolide antibiotics) Increased brigatinib levels (CYP3A4 inhibition) Avoid strong CYP3A4 inhibitors; consider alternative antibiotics
Alfentanil, fentanyl (opioid analgesics) Complex interaction via CYP3A4 pathway Use with caution; monitor for increased opioid effects

This is not a complete list of all possible drug interactions. Always inform your doctor and pharmacist about every medicine you are taking, including prescription drugs, over-the-counter medications, vitamins, and herbal supplements. Your doctor will evaluate potential interactions and may adjust your treatment plan accordingly.

What Is the Correct Dosage of Alunbrig?

Quick Answer: The recommended starting dose is one 90 mg tablet once daily for the first 7 days, followed by one 180 mg tablet once daily thereafter. Tablets are taken with or without food. Your doctor may adjust the dose depending on side effects, and 30 mg tablets are available for dose reductions.

Always take Alunbrig exactly as your doctor or pharmacist has told you. Do not change your dose without consulting your doctor first. The dose may need to be adjusted based on how well you tolerate the medication.

Adults

Standard Dosing Schedule

Week 1 (Days 1–7): One 90 mg tablet once daily

Week 2 onwards: One 180 mg tablet once daily

The lower starting dose during the first week is specifically designed to reduce the risk of early-onset pulmonary adverse events. Do not skip the lead-in period or start directly at the 180 mg dose.

Starter Pack

When beginning treatment, your doctor may prescribe a starter pack. Each starter pack contains an outer carton with two inner cartons:

  • 7 film-coated 90 mg tablets (for the first week)
  • 21 film-coated 180 mg tablets (for weeks 2–4)

The required dose is printed on the starter pack to help you follow the correct dosing schedule.

How to Take Alunbrig

  • Take Alunbrig once daily at the same time each day
  • Swallow the tablets whole with a glass of water
  • Do not crush, break, or dissolve the tablets
  • You may take the tablets with or without food
  • If you vomit after taking a dose, do not take an extra tablet; take the next dose at the usual scheduled time
  • Do not swallow the desiccant container found inside the bottle

Dose Adjustments

Your doctor may reduce your dose if you experience significant side effects. The 30 mg tablets are available to allow for flexible dose adjustments. Possible dose reductions follow this pattern:

Dose Reduction Levels for Alunbrig
Dose Level During Lead-in (Days 1–7) After Lead-in (Day 8+)
Standard dose 90 mg once daily 180 mg once daily
First reduction 60 mg once daily 120 mg once daily
Second reduction 30 mg once daily 90 mg once daily
Third reduction 60 mg once daily

If the lowest dose is not tolerated, your doctor will discontinue Alunbrig treatment.

Children

Alunbrig has not been studied in children and adolescents under 18 years of age. It is not recommended for use in this population. The safety and efficacy of brigatinib in pediatric patients have not been established.

Elderly Patients

No specific dose adjustment is required based on age alone. Clinical trials included patients aged 65 years and older, and no significant differences in safety or efficacy were observed compared to younger patients. However, elderly patients may be more susceptible to certain side effects, and your doctor will monitor you closely.

Missed Dose

If you miss a dose or vomit after taking a dose, do not take a double dose to compensate. Simply take the next dose at the usual scheduled time. Continue with your regular dosing schedule.

Overdose

If you take more tablets than recommended, tell your doctor or pharmacist immediately. There is no specific antidote for brigatinib overdose. Treatment is supportive and based on the symptoms experienced.

Do Not Stop Treatment Without Medical Advice

Do not stop taking Alunbrig without first discussing it with your doctor. Stopping treatment prematurely may allow the cancer to progress. If you have any concerns about your treatment, discuss them with your oncology team.

What Are the Side Effects of Alunbrig?

Quick Answer: The most common side effects of Alunbrig include high blood pressure, elevated creatine phosphokinase, visual disturbances, elevated pancreatic and liver enzymes, hyperglycemia, diarrhea, nausea, fatigue, cough, headache, and rash. Serious side effects include early-onset pulmonary events (especially in the first week), bradycardia, and pancreatitis.

Like all medicines, Alunbrig can cause side effects, although not everyone gets them. Some side effects may be serious and require immediate medical attention. Your doctor may need to adjust your dose, temporarily interrupt treatment, or discontinue Alunbrig depending on the severity of side effects.

Serious Side Effects Requiring Immediate Medical Attention

Very Common (Serious)

May affect more than 1 in 10 people

  • High blood pressure (hypertension): headache, dizziness, blurred vision, chest pain, or shortness of breath
  • Visual disturbances: flashes of light, blurred vision, or sensitivity to light – your doctor may refer you to an ophthalmologist
  • Elevated creatine phosphokinase (CPK): may indicate muscle damage – report unexplained muscle pain, tenderness, or weakness
  • Elevated amylase or lipase: may indicate pancreatic inflammation – report upper abdominal pain, pain worsening after eating, weight loss, or nausea
  • Elevated liver enzymes (AST, ALT): may indicate liver cell damage – report right-sided abdominal pain, jaundice, or dark urine
  • Hyperglycemia (high blood sugar): excessive thirst, frequent urination, increased hunger, nausea, weakness, fatigue, or confusion

Common (Serious)

May affect up to 1 in 10 people

  • Pneumonitis / interstitial lung disease: new or worsening breathing problems, chest pain, cough, and fever – especially during the first week of treatment
  • Bradycardia (slow heartbeat): chest discomfort, irregular heartbeat, dizziness, lightheadedness, or fainting
  • Photosensitivity (sun sensitivity): skin reaction after sun exposure

Uncommon (Serious)

May affect up to 1 in 100 people

  • Pancreatitis: severe and persistent abdominal pain, with or without nausea and vomiting

Other Side Effects

Very Common

May affect more than 1 in 10 people

  • Pneumonia (lung infection)
  • Upper respiratory tract infection (cold symptoms)
  • Decreased red blood cells (anemia)
  • Decreased white blood cells (neutropenia, lymphopenia)
  • Prolonged blood clotting time (activated partial thromboplastin time)
  • Elevated insulin and calcium in blood tests
  • Decreased phosphorus, magnesium, sodium, and potassium in blood tests
  • Decreased appetite
  • Headache
  • Peripheral neuropathy (numbness, tingling, weakness, or pain in hands or feet)
  • Dizziness
  • Cough
  • Shortness of breath (dyspnea)
  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal pain
  • Constipation
  • Mouth and lip inflammation (stomatitis)
  • Elevated alkaline phosphatase in blood tests
  • Rash
  • Itching (pruritus)
  • Joint or muscle pain (including muscle spasms)
  • Elevated creatinine in blood tests (may indicate reduced kidney function)
  • Fatigue
  • Edema (swelling due to fluid retention)
  • Fever

Common

May affect up to 1 in 10 people

  • Low platelet count (thrombocytopenia), increasing risk of bleeding and bruising
  • Sleep difficulties (insomnia)
  • Memory impairment
  • Altered taste sensation
  • Prolonged QT interval on ECG (abnormal heart electrical activity)
  • Rapid heartbeat (tachycardia)
  • Palpitations
  • Dry mouth
  • Indigestion (dyspepsia)
  • Flatulence
  • Elevated lactate dehydrogenase in blood tests
  • Elevated bilirubin in blood tests
  • Dry skin
  • Musculoskeletal chest pain
  • Pain in arms and legs
  • Muscle and joint stiffness
  • Chest pain and discomfort
  • Pain
  • Elevated cholesterol in blood tests
  • Weight loss

If you experience any side effects, including those not listed here, tell your doctor or pharmacist. You can also report suspected side effects to your national pharmacovigilance authority (e.g., the EMA in Europe, the FDA MedWatch program in the United States, or the MHRA Yellow Card Scheme in the United Kingdom) to help monitor the ongoing benefit-risk profile of Alunbrig.

How Should You Store Alunbrig?

Quick Answer: Store Alunbrig at room temperature with no special storage requirements. Keep out of the reach and sight of children. Do not use after the expiry date printed on the packaging. Leave the desiccant container in the bottle. Dispose of unused medication according to your pharmacist’s instructions.

Keep Alunbrig out of the sight and reach of children at all times. Do not use this medicine after the expiry date stated on the bottle label, blister packaging, or carton after “EXP.” The expiry date refers to the last day of the stated month.

  • Storage conditions: No special storage requirements. Store at room temperature.
  • Desiccant: If your tablets come in a bottle, leave the desiccant container inside the bottle to protect the tablets from moisture. Do not swallow the desiccant.
  • Disposal: Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help protect the environment.

What Does Alunbrig Contain?

Quick Answer: The active substance is brigatinib, available in 30 mg, 90 mg, and 180 mg film-coated tablets. Inactive ingredients include lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, colloidal anhydrous silica, magnesium stearate, and a film coating of talc, macrogol, polyvinyl alcohol, and titanium dioxide.

Active Substance

The active substance in Alunbrig is brigatinib. Each tablet contains a specific amount of brigatinib depending on the strength:

  • 30 mg tablet: Each film-coated tablet contains 30 mg brigatinib
  • 90 mg tablet: Each film-coated tablet contains 90 mg brigatinib
  • 180 mg tablet: Each film-coated tablet contains 180 mg brigatinib

Inactive Ingredients (Excipients)

  • Lactose monohydrate
  • Microcrystalline cellulose
  • Sodium starch glycolate (type A)
  • Colloidal anhydrous silica
  • Magnesium stearate
  • Talc
  • Macrogol
  • Polyvinyl alcohol
  • Titanium dioxide

Appearance and Pack Sizes

Alunbrig film-coated tablets are white to off-white in color. The 90 mg and 180 mg tablets are oval-shaped, while the 30 mg tablets are round. All tablets have convex surfaces on both sides.

  • 30 mg tablets: Approximately 7 mm in diameter, debossed with “U3” on one side and plain on the other
  • 90 mg tablets: Approximately 15 mm long, debossed with “U7” on one side and plain on the other
  • 180 mg tablets: Approximately 19 mm long, debossed with “U13” on one side and plain on the other

Alunbrig is available in blister packs and in bottles with child-resistant closures. Pack sizes include:

  • 30 mg: 28, 56, or 112 tablets (blisters); 60 or 120 tablets (bottles)
  • 90 mg: 7 or 28 tablets (blisters); 7 or 30 tablets (bottles)
  • 180 mg: 28 tablets (blisters); 30 tablets (bottles)

Not all pack sizes may be available in your country. A starter pack is also available containing 7 tablets of 90 mg and 21 tablets of 180 mg for the first month of treatment.

Manufacturer

Alunbrig is marketed by Takeda. Manufacturing is performed by Takeda Austria GmbH, Linz, Austria, and Takeda Ireland Limited, Bray, Ireland. The marketing authorization holder is Takeda Pharma A/S, Vallensbaek Strand, Denmark.

Frequently Asked Questions About Alunbrig

Alunbrig (brigatinib) is used to treat adults with advanced ALK-positive non-small cell lung cancer (NSCLC). It can be used as a first-line treatment (in patients not previously treated with an ALK inhibitor) or in patients who have previously been treated with crizotinib. ALK-positive NSCLC is identified through molecular testing of the tumor, and represents approximately 3–5% of all non-small cell lung cancers.

The step-up dosing schedule (90 mg for 7 days, then 180 mg) was specifically designed to reduce the risk of early-onset pulmonary adverse events, which are more common during the first week of treatment with brigatinib. By starting at a lower dose, the body has time to adjust to the medication, significantly reducing the incidence of these lung-related side effects. It is important not to skip this lead-in period or start at the higher dose.

Yes, one of the key advantages of Alunbrig is its notable efficacy against brain (intracranial) metastases. In the ALTA-1L clinical trial, brigatinib demonstrated a confirmed intracranial response rate of 78% in patients with measurable brain metastases, compared to 26% with crizotinib. Brain metastases are a common complication of ALK-positive lung cancer, and brigatinib’s ability to cross the blood-brain barrier and achieve therapeutic concentrations in the CNS makes it a particularly valuable treatment option for these patients.

Grapefruit and grapefruit juice contain compounds called furanocoumarins that inhibit the CYP3A4 enzyme in your gut and liver. This enzyme is one of the pathways involved in breaking down brigatinib. When CYP3A4 is inhibited, more brigatinib is absorbed into the bloodstream, leading to higher drug levels than intended. This can increase the risk and severity of side effects. You should avoid all grapefruit products – including grapefruit, grapefruit juice, and marmalade – throughout your entire course of treatment.

In the pivotal ALTA-1L trial comparing brigatinib to crizotinib as first-line treatment for ALK-positive NSCLC, brigatinib demonstrated significantly superior progression-free survival. The estimated 3-year progression-free survival rate was 43% with brigatinib compared to 19% with crizotinib. Brigatinib also showed superior intracranial efficacy. Compared to other next-generation ALK inhibitors (such as alectinib and lorlatinib), cross-trial comparisons suggest broadly similar efficacy, though direct head-to-head trials have not been conducted. The choice among ALK inhibitors is made by your oncologist based on individual patient factors.

If you have kidney problems or are receiving dialysis, tell your doctor before starting Alunbrig. Your doctor may need to adjust your dose or monitor you more closely. Symptoms of kidney problems can include nausea, changes in urination patterns, and abnormal blood test results. For patients with mild to moderate liver impairment, no dose adjustment is typically needed, but liver function will be monitored regularly through blood tests. Discuss your specific situation with your doctor, who will determine the most appropriate approach for you.

References

  1. European Medicines Agency (EMA). Alunbrig (brigatinib) – Summary of Product Characteristics. Last updated 2025. Available from: EMA EPAR.
  2. U.S. Food and Drug Administration (FDA). Alunbrig (brigatinib) Prescribing Information. Revised 2024. Available from: FDA Drug Label.
  3. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib Versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer (ALTA-1L). N Engl J Med. 2018;379(21):2027–2039. doi:10.1056/NEJMoa1810171.
  4. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. J Thorac Oncol. 2021;16(12):2091–2108. doi:10.1016/j.jtho.2021.07.035.
  5. Huber RM, Hansen KH, Paz-Ares Rodriguez L, et al. Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial. J Thorac Oncol. 2020;15(3):404–415. doi:10.1016/j.jtho.2019.11.004.
  6. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2025.
  7. Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(1):52–94.
  8. World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
  9. Solomon BJ, Bauer TM, Mok TSK, et al. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023;11(4):354–366.
  10. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):829–838. doi:10.1056/NEJMoa1704795.

Editorial Team

This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in thoracic oncology, pulmonology, and clinical pharmacology.

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iMedic Oncology Editorial Team – specialist physicians in thoracic oncology with clinical experience in ALK-positive lung cancer treatment

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