Sotorasib is a precise targeted therapeutic agent for KRAS G12C mutations, indicated for patients with specific genotypes of lung cancer and colorectal cancer.

I. Indications

Locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutation

As monotherapy, it is indicated for adult patients with non-small cell lung cancer confirmed to harbor KRAS G12C mutation via an FDA-approved assay, who have experienced disease progression following at least one prior systemic therapy.

Metastatic colorectal cancer with KRAS G12C mutation

In combination with panitumumab, it is indicated for adult patients with metastatic colorectal cancer confirmed to harbor KRAS G12C mutation via an FDA-approved assay, who have previously received chemotherapy regimens based on fluoropyrimidine, oxaliplatin and irinotecan.

Pre-treatment testing requirements

(1) For patients with lung cancer, KRAS G12C mutation testing may be performed using tumor tissue or plasma specimens. If no mutation is detected in plasma samples, tumor tissue testing is required.

(2) For patients with colorectal cancer, testing must be conducted using tumor tissue specimens.

II. Contraindications

Official contraindications

None. However, this does not mean the drug is suitable for all individuals; administration still requires assessment based on individual health conditions.

Drug classes to avoid concomitant use

The following agents are not absolute contraindications, but concomitant administration with sotorasib should be avoided, as such combination may reduce drug efficacy or increase toxicities:

(1) Proton pump inhibitors (e.g., omeprazole, lansoprazole, pantoprazole, esomeprazole). These agents significantly reduce the plasma concentration of sotorasib.

(2) H2 receptor antagonists (e.g., famotidine, cimetidine, ranitidine), which similarly impair drug absorption.

(3) Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John’s wort). These agents accelerate the metabolism of sotorasib and attenuate its therapeutic effect.

Precautions for use of topical antacids

If locally acting antacids such as magnesium aluminum carbonate and aluminum hydroxide are clinically necessary, they should be administered at an interval from sotorasib:

Administer sotorasib first, followed by the antacid 4 hours later; or administer the antacid first, followed by sotorasib 10 hours later.

III. Special Population Administration

Pregnant women

Women of childbearing potential are advised to adopt effective contraception throughout the treatment period.

Breastfeeding women

Breastfeeding is not recommended.

Pediatric patients

Use is not recommended.

Elderly patients

No significant differences in safety and efficacy have been observed between elderly and younger patients; no dose adjustment is required.

Patients with hepatic impairment

(1) No dose adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh Class A or B).

(2) The impact of severe hepatic impairment (Child-Pugh Class C) on the safety of sotorasib remains unclear. More frequent monitoring of adverse reactions, particularly hepatotoxicity, is required.

Patients with renal impairment

(1) No dose adjustment is required for patients with mild and moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m²).

(2) The pharmacokinetic effects of severe renal impairment have not been investigated; caution is advised when prescribing this drug.