ALK inhibitors tailored for oncology pharmacists, highlighting differences in CNS penetration, toxicity, and monitoring—perfect for BPS exam prep:
| Feature | Crizotinib | Ceritinib | Alectinib | Lorlatinib |
|---|---|---|---|---|
| Generation | 1st | 2nd | 2nd | 3rd |
| Indication | ALK+ NSCLC, first-line | ALK+ NSCLC, 1st-line or after crizotinib | ALK+ NSCLC, first-line or after crizotinib | ALK+ NSCLC after 2nd-gen ALK TKI failure; CNS disease |
| CNS Penetration | Limited | Moderate | Good | Excellent |
| Mechanism | ALK, ROS1 inhibitor | ALK inhibitor | ALK inhibitor | ALK & ROS1 inhibitor, crosses BBB, effective against resistance mutations |
| Dose | 250 mg PO BID | 450–750 mg PO daily (fasted) | 600 mg PO BID | 100 mg PO daily |
| Key Toxicities / ADRs | Visual disturbances, edema, GI toxicity, hepatotoxicity, QT prolongation | GI toxicity (diarrhea, nausea), hepatotoxicity, fatigue | Fatigue, myalgia, edema, hepatotoxicity | Hyperlipidemia, CNS effects (cognitive, mood), edema, hepatotoxicity, neuropathy |
| Metabolism / Interactions | CYP3A4 substrate | CYP3A4 substrate | CYP3A4 substrate | CYP3A4 substrate; moderate P-gp inhibitor |
| Monitoring / Pharmacist Considerations | LFTs, ECG (QT), edema, visual changes | LFTs, GI toxicity, drug interactions | LFTs, CPK (myalgia), edema | Lipids, LFTs, neurologic assessment, edema, drug interactions |
| Clinical Pearls | First-gen, lower CNS activity → CNS metastases often progress | Use after crizotinib progression; GI toxicity may limit dose | Good CNS penetration; generally well tolerated; often first-line preferred over crizotinib | Reserved for resistant disease or CNS metastases; monitor neurotoxicity and hyperlipidemia |
Quick Takeaways for BPS Exam
- First-line ALK therapy: typically alectinib (preferred over crizotinib due to CNS activity and better PFS).
- Crizotinib: first-gen; limited CNS penetration → brain metastases common.
- Second-gen ALK inhibitors (ceritinib, alectinib): better CNS activity; alectinib is well tolerated.
- Third-gen (lorlatinib): used after resistance to 2nd-gen ALK inhibitors; excellent CNS penetration; CNS and metabolic toxicities more prominent.
- Pharmacist role: monitor LFTs, ECG, lipids, neurologic symptoms, edema, and manage CYP3A4-mediated interactions.