Class: 3rd-generation ALK and ROS1 tyrosine kinase inhibitor (TKI).
Indication:
- ALK-positive metastatic NSCLC, including patients previously treated with ≥1 ALK TKI (e.g., crizotinib, alectinib, ceritinib, brigatinib).
- ROS1-positive NSCLC (off-label in some regions).
Dose: 100 mg orally once daily (with or without food).
Key Pharmacology:
- Potent CNS penetration → effective against brain metastases.
- Overcomes resistance mutations (e.g., G1202R).
Adverse Effects:
- CNS effects: cognitive, mood, speech disturbances.
- Hyperlipidemia (very common → often requires lipid-lowering therapy).
- Peripheral neuropathy, edema, weight gain, hypertension.
- Rare: ILD/pneumonitis, AV block.
Monitoring:
- Baseline and periodic lipid profile (esp. cholesterol & triglycerides).
- Blood pressure, weight, CNS status.
- ECG if cardiac risk.
Drug Interactions:
- CYP3A substrate & moderate inducer → avoid strong CYP3A inducers/inhibitors.
- Can reduce efficacy of sensitive CYP3A substrates (e.g., some immunosuppressants, hormonal contraceptives).