Sotorasib – KRAS G12C Inhibitor Therapy

Sotorasib is a first-in-class targeted anti-cancer medication designed to inhibit a specific KRAS protein mutation, which was long considered "undruggable." This drug provides a significant breakthrough for patients with genetically driven forms of lung cancer.

The mechanism of action involves irreversible and selective binding to the mutant KRAS G12C protein. This mutation keeps the protein in a perpetually active ("on") state, driving uncontrolled cell division. Sotorasib locks the protein in its inactive state, interrupting the signaling cascade necessary for tumor survival and growth. The drug specifically targets G12C-mutant cells while sparing healthy cells with normal (wild-type) KRAS proteins.

Sotorasib is administered orally as tablets once daily, providing systemic therapy for tumor lesions.

Wikipedia page

Indications

Sotorasib is indicated for the treatment of adult patients with the following condition:

KRAS G12C-mutated NSCLC: locally advanced or metastatic non-small cell lung cancer with a confirmed KRAS G12C mutation.
Line of Therapy: used in patients who have received at least one prior systemic anti-cancer therapy.

Dosage and administration

Sotorasib administration requires strict adherence to the schedule and monitoring of liver function.

Standard Dose: 960 mg (eight 120 mg tablets) taken once daily.
Administration Rules: tablets should be swallowed whole, with or without food, at the same time each day.
Antacid Interaction: avoid co-administration with proton pump inhibitors or H2 blockers, as they can significantly reduce drug absorption.
Dose Modification: if adverse reactions occur, the dose may be reduced to 480 mg or 240 mg daily.

The use of sotorasib is restricted in the following cases:

Hypersensitivity: severe allergic reactions to sotorasib or any of its components.
Pregnancy and Lactation: not recommended due to potential fetal risk; breastfeeding should be discontinued during treatment.
Pediatric Use: safety and efficacy in children and adolescents have not been established.
Liver Impairment: requires careful clinical assessment in patients with pre-existing hepatic issues.

The most common adverse reactions associated with sotorasib therapy include:

Gastrointestinal: diarrhea (the most frequent side effect), nausea, vomiting, and abdominal pain.
Hepatic: hepatotoxicity (elevated ALT and AST levels), requiring regular blood monitoring.
Musculoskeletal: joint pain (arthralgia) and muscle pain (myalgia).
General: fatigue, dyspnea (shortness of breath), and cough.
Laboratory: decreased hemoglobin levels and electrolyte imbalances.

Frequently Asked Questions

Sotorasib is the world's first selective and irreversible inhibitor of the KRAS G12C protein. For decades, KRAS mutations were considered "undruggable" due to the lack of clear binding sites for medication. Sotorasib specifically binds to the mutant protein in its inactive state, shutting down the signaling pathways that drive uncontrolled cancer cell division.

The substance is indicated specifically for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation. It is typically prescribed after a patient has received at least one prior line of systemic therapy, such as chemotherapy or immunotherapy.

Sotorasib acts only on the G12C mutation and is not effective against other KRAS mutations or in their absence. A genetic analysis of the tumor or a liquid biopsy is essential for the physician to confirm that the drug will hit the specific molecular target in the patient's body.

Tablets should be taken once daily at the same time, with or without food. They should be swallowed whole. For patients with difficulty swallowing, the tablets can be dispersed in a glass of non-carbonated water (without mechanical crushing), stirred until a suspension forms, and consumed immediately.

The most common side effects include diarrhea, nausea, and increased liver enzyme levels (ALT/AST). During therapy, liver function tests will be performed regularly. If significant elevations occur, the physician may temporarily withhold the medication or reduce the dose.