Side Effects of Afatinib
The most common adverse effects of afatinib are gastrointestinal (diarrhea and stomatitis/mucositis) and cutaneous (rash, dry skin, and paronychia), with the majority of patients experiencing diarrhea and approximately 70-80% experiencing skin-related toxicities. 1
Common Adverse Events (All Grades)
Gastrointestinal Effects
- Diarrhea: Occurs in 70-87% of patients 1, 2, 3
- Stomatitis/Mucositis: 13-36.5% of patients 2, 3
- Grade 3-4 in approximately 2.1% 3
- Nausea: 21% 2
- Vomiting: 13% 2
- Decreased appetite: 25% 2
Cutaneous/Dermatologic Effects
- Rash/Acneiform dermatitis: 27-71.4% of patients 2, 3
- Paronychia (nail infection): 31-52.1% 2, 3
- Grade 3-4 in 3.8% 3
- Pruritus: 10-13% 2
- Nail disorders: 2.8-9.2% 2
Laboratory Abnormalities
- Increased alkaline phosphatase: 34% (Grade 3-4: 2%) 2
- Decreased white blood cell count: 12% (Grade 3-4: 1%) 2
- Decreased potassium: 11% (Grade 3-4: 1%) 2
- Increased ALT: 10% (Grade 3-4: 1%) 2
- Increased AST: 7% (Grade 3-4: 1%) 2
Serious Adverse Events
Serious adverse reactions occurred in 44% of patients treated with afatinib 2. The most frequent serious adverse reactions include:
- Pneumonia (6.6%)
- Diarrhea (4.6%)
- Dehydration (3.1%)
- Dyspnea (3.1%)
Fatal Adverse Events
Fatal adverse reactions are rare but include 2:
- Interstitial lung disease (0.5%)
- Pneumonia (0.3%)
- Respiratory failure (0.3%)
- Acute renal failure (0.3%)
- General physical health deterioration (0.3%)
Postmarketing Serious Reactions
Additional serious adverse events identified after approval 2:
- Pancreatitis
- Toxic epidermal necrolysis/Stevens-Johnson syndrome
Treatment Modifications
Dose reductions were required in 27% of patients and discontinuation in 20% due to adverse events 2. The most common reasons for:
Dose Reduction:
- Diarrhea (15%)
- Rash/acne (5.9%)
- Stomatitis (3.1%)
Discontinuation:
- Diarrhea (4.1%)
- Rash/acne (2.6%)
Important Clinical Context
While these adverse events are common, they are usually mild and manageable with appropriate supportive care 1. The guideline emphasizes that when moderate or severe, these toxicities can negatively impact quality of life and lead to dose modifications 1.
Close monitoring is essential, particularly bi-weekly during the first 6 weeks of treatment, then monthly thereafter 1. This proactive approach allows for early intervention with supportive medications, treatment delays, and dose reductions to maintain patients on therapy and preserve clinical benefit 1.
Key Management Principles:
- For diarrhea: Low-fat, low-fiber diet; loperamide with oral isotonic solution for persistent diarrhea >48 hours 1
- For cutaneous effects: Regular emollients, topical corticosteroids/antibiotics, and oral antibiotics as needed 1
- Dose reduction or interruption is appropriate for prolonged or intolerable Grade 2 toxicity 1