Sotorasib (Specialist drug)

How it works

It binds irreversibly and selectively to the mutant KRAS G12C protein, locking it in an inactive state and blocking the downstream proliferative signalling driven by this oncogenic mutation.

Prescribing in practice

• Hepatotoxicity is a key risk, so liver function must be checked before and during treatment and the drug interrupted or stopped for significant transaminase rises.
• It can cause drug-induced interstitial lung disease/pneumonitis, which should prompt urgent assessment and withholding of therapy.
• Acid-reducing agents and CYP3A4 inducers reduce sotorasib exposure, so co-prescribing should be reviewed against the SPC.

Monitoring

Monitor liver function tests regularly and watch for new or worsening respiratory symptoms suggestive of pneumonitis.

Counselling the patient

• Report yellowing of the skin or eyes, dark urine, or new breathlessness and cough promptly.
• Tell your team about all other medicines, including antacids and indigestion remedies, as they can reduce how well this drug works.
• Take the tablets as directed and attend regular blood tests.

Evidence & guidelines

Efficacy in pretreated KRAS G12C-mutated non-small-cell lung cancer was demonstrated in dedicated registrational trials and is reflected in NICE guidance.