Adagrasib (Krazati): KRAS G12C Inhibitor for NSCLC
Adagrasib is a highly selective and potent oral small-molecule inhibitor of KRAS G12C. For decades, KRAS mutations were considered "undruggable targets" in oncology. Adagrasib (Krazati) represents a major breakthrough in personalized medicine for lung cancer.
The drug works by covalently binding to the mutant KRAS G12C protein and locking it in an inactive state. This prevents the downstream signaling that drives tumor growth and cell survival. It is designed to penetrate the central nervous system, which is crucial as lung cancer often metastasizes to the brain.
It is indicated for patients whose cancer has progressed despite previous standard treatments.
Indications
- Non-Small Cell Lung Cancer (NSCLC): Treatment of adult patients with locally advanced or metastatic NSCLC.
- Biomarker Requirement: Specifically approved for tumors harboring the KRAS G12C mutation, as determined by an FDA-approved test.
- Prior Therapy: Indicated for patients who have received at least one prior systemic therapy (chemotherapy or immunotherapy).
Dosage and administration
Consistency in timing is key for efficacy.
- Recommended Dose: 600 mg (typically three 200 mg tablets) taken orally twice daily. Total daily dose is 1200 mg.
- Administration: Swallow tablets whole with or without food. Do not chew, crush, or split tablets.
- Vomiting: If vomiting occurs after taking a dose, do not take an additional dose. Resume with the next scheduled dose.
- Interstitial Lung Disease (ILD): Contraindicated or requires discontinuation if ILD/pneumonitis is confirmed.
- Pregnancy and Breastfeeding: Can cause fetal harm.
- Severe hypersensitivity to adagrasib.
Gastrointestinal and hepatic monitoring is essential.
- Gastrointestinal: Diarrhea (very common), nausea, vomiting. Anti-diarrheal medication and hydration are often recommended.
- Hepatotoxicity: Elevated liver enzymes (ALT, AST). Regular blood tests are mandatory.
- Cardiac: QTc interval prolongation.
- Other: Fatigue, musculoskeletal pain, renal impairment (increased creatinine).
