Alectinib

• 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.