Camatinib is a targeted therapy primarily used to treat a specific type of metastatic non-small cell lung cancer (NSCLC)—patients with tumor mutations causing mesenchymal-epithelial transition (MET) exon 14 skipping. Understanding the correct dosage and administration ensures the drug targets the tumor precisely for optimal therapeutic effect.
1. Patient Selection
Patients should be selected for carmatinib treatment based on the presence of mutations causing MET exon 14 skipping in tumor or plasma samples. If no mutation causing MET exon 14 skipping is detected in plasma samples, tumor tissue should be tested if feasible.
2. Recommended Dosage
The recommended dose of carmatinib is 400 mg orally twice daily, with or without food.
Carmatinib tablets must be swallowed whole; do not break, crush, or chew them.
If a patient misses a dose or vomits after taking the medication, they should be informed that no make-up dose is needed and the next dose should be taken at the originally scheduled time.
3. Dosage Adjustment for Adverse Reactions
The recommended dose reduction protocol for adverse reaction management is as follows: The initial dose reduction is 300 mg orally twice daily; the second dose reduction is 200 mg orally twice daily. For patients who cannot tolerate the 200 mg twice-daily oral dose, carmatinib should be permanently discontinued.
Specific recommended dose adjustments for adverse reactions are as follows:
(Abbreviations: ALT = alanine aminotransferase, AST = aspartate aminotransferase, ILD = interstitial lung disease, ULN = upper limit of normal; severity grading is based on the Common Terminology Standard for Adverse Events (CTCAE) version 5.0):
Interstitial Lung Disease (ILD)/Pneumonia
Carmatinib should be permanently discontinued for any grade.
Elevated ALT and/or AST (without elevated total bilirubin)
Carmatinib should be discontinued for grade 3 until ALT/AST returns to baseline levels. If bilirubin levels return to baseline within 7 days, treatment can be restarted at the original dose; otherwise, the dose must be reduced before restarting. Carmatinib is permanently discontinued at Grade 4.
Elevated ALT and/or AST with elevated total bilirubin (without cholestasis or hemolysis)
When ALT and/or AST > 3 times the ULN and total bilirubin > 2 times the ULN, carmatinib is permanently discontinued.
Elevated total bilirubin (without simultaneous elevation of ALT and/or AST)
Carmatinib is suspended at Grade 2 until bilirubin returns to baseline levels. If bilirubin levels return to baseline within 7 days, treatment can be restarted at the original dose; otherwise, the dose must be reduced before restarting. Carmatinib is suspended at Grade 3 until bilirubin returns to baseline levels. If bilirubin levels return to baseline within 7 days, treatment can be restarted at a reduced dose; otherwise, it is permanently discontinued. Carmatinib is permanently discontinued at Grade 4.
Elevated lipase or amylase
Carmatinib is suspended at Grade 3 until the levels decrease to ≤ Grade 2 or baseline levels. If recovery to baseline or ≤ grade 2 occurs within 14 days, the dose can be reduced and restarted; otherwise, permanent discontinuation is required. Carmatinib is permanently discontinued at grade 4.
Pancreatitis
Carmatinib is permanently discontinued at grade 3 or 4.
Hypersensitivity
If hypersensitivity is suspected based on clinical judgment, suspend carmatinib until the reaction resolves. Patients experiencing severe hypersensitivity should permanently discontinue carmatinib.
Other Adverse Reactions
At grade 2, maintain the current dose; if intolerable, treatment can be suspended until resolution, followed by a dose reduction and restart. At grade 3, treatment can be suspended until resolution, followed by a dose reduction and restart. Carmatinib is permanently discontinued at grade 4.
