- Class: Tyrosine kinase inhibitor – ALK inhibitor (small molecule, second-generation)
Mechanism of Action (MOA)
- Selectively inhibits anaplastic lymphoma kinase (ALK) tyrosine kinase.
- Blocks ALK-mediated signaling pathways (RAS/RAF/MEK/ERK, PI3K/AKT, JAK/STAT).
- Causes cell cycle arrest and apoptosis in ALK-positive tumor cells.
- Active against crizotinib-resistant ALK mutations.
- Good CNS penetration, effective against brain metastases.
Clinical Uses
- ALK-positive metastatic or locally advanced NSCLC:
- First-line therapy in newly diagnosed patients.
- Alternative after progression on crizotinib.
Dosing (Adults)
- 600 mg orally twice daily (with food).
- Dose adjustments for:
- Severe hepatic impairment
- Drug interactions (CYP3A inhibitors/inducers)
Toxicities
- Hepatotoxicity – ↑ AST/ALT, bilirubin; monitor LFTs.
- Fatigue, myalgia, edema, constipation.
- Bradycardia (rare), ECG changes uncommon.
- Rash (mild), nausea.
- Pulmonary toxicity (rare interstitial lung disease).
- Less GI toxicity compared to ceritinib.
Monitoring
- Liver function tests (AST, ALT, bilirubin) regularly.
- ECG for bradycardia or conduction abnormalities if clinically indicated.
- Signs of pulmonary toxicity (dyspnea, cough).
- CBC, renal function as needed.
Summary
Alectinib (Alecensa®) is a second-generation ALK inhibitor for ALK-positive NSCLC, including patients with CNS metastases. Key monitoring includes hepatotoxicity, pulmonary toxicity, and bradycardia, with fewer GI side effects compared to ceritinib.