What are the potential side effects of brigatinib (Alunbrig)?

Side Effects of Brigatinib (Alunbrig)

Brigatinib commonly causes fatigue, gastrointestinal issues, muscle problems, respiratory symptoms, and laboratory abnormalities, with the most serious concern being early-onset pulmonary events that can occur within the first week of treatment.

Common Side Effects

Brigatinib has several common side effects that patients should be aware of:

Gastrointestinal Effects

• Diarrhea (53% of patients)
• Nausea (30%)
• Vomiting (21%)
• Abdominal pain (24%)
• Constipation (18%) 1

Respiratory Effects

• Cough (35%)
• Dyspnea/shortness of breath (25%)
• Interstitial lung disease (ILD)/pneumonitis (4-5%) - a potentially serious adverse effect 2, 1

Musculoskeletal Effects

• Increased creatine phosphokinase levels (81%) - indicating potential muscle damage
• Myalgia/muscle pain (28%) 1

Cardiovascular Effects

• Hypertension (32%)
• Bradycardia (12%) 1

Other Common Effects

• Fatigue (32%)
• Rash (40%)
• Headache (22%)
• Edema/fluid retention (18%)
• Pruritus/itching (20%) 1

Serious Side Effects Requiring Immediate Attention

Early-Onset Pulmonary Events

• Occurs within the first 7 days of treatment in approximately 3-8% of patients
• Symptoms include shortness of breath, cough, chest pain, fever
• Can be severe or life-threatening
• Risk factors include older age, poorer performance status, and higher number of previous treatment regimens 3, 2

Other Serious Concerns

• Visual disturbances (7.4%) - may require ophthalmologic evaluation
• Hyperglycemia - blood sugar monitoring is recommended
• Hepatotoxicity - liver enzyme monitoring is required
• Pancreatitis - amylase and lipase monitoring is needed 1

Laboratory Abnormalities

Brigatinib frequently causes laboratory abnormalities that require monitoring:

• Increased creatine phosphokinase (81% of patients, 24% grade 3-4)
• Increased lipase (59%, 17% grade 3-4)
• Increased aspartate aminotransferase (72%, 4.5% grade 3-4)
• Hyperglycemia (56%, 7.5% grade 3-4)
• Increased alanine aminotransferase (52%, 5% grade 3-4) 1

Risk Mitigation Strategies

Dosing Strategy

• Brigatinib uses a step-up dosing approach to reduce risk of pulmonary events:
  • Start with 90 mg once daily for 7 days
  • If tolerated, increase to 180 mg once daily 1, 2

Monitoring Recommendations

• Close monitoring during the first week for pulmonary symptoms
• Regular blood pressure monitoring
• Periodic laboratory testing (liver enzymes, pancreatic enzymes, blood glucose, CPK)
• Heart rate monitoring for bradycardia
• Vision assessment for visual disturbances 1

Precautions

• Avoid grapefruit juice (increases brigatinib plasma concentration)
• Limit sun exposure and use sun protection (SPF ≥30) due to photosensitivity
• Use effective contraception during treatment and for 4 months (females) or 3 months (males) after the final dose 1

Comparative Safety Profile

When compared to other ALK inhibitors like crizotinib:

• Brigatinib has higher rates of increased CPK, hypertension, and rash
• Lower rates of visual disturbances compared to crizotinib (7.4% vs 53%)
• Early-onset pulmonary events are relatively unique to brigatinib 2

Management of Side Effects

• For ILD/pneumonitis: Withhold brigatinib, evaluate symptoms, consider corticosteroids, and adjust dose or discontinue based on severity
• For hypertension: Antihypertensive therapy and dose modification as needed
• For elevated enzymes: Monitor and adjust dose based on severity
• For gastrointestinal effects: Supportive care with antiemetics and antidiarrheals as needed 1

Remember to report any new or worsening symptoms to your healthcare provider immediately, especially respiratory symptoms occurring within the first week of treatment.