Lorlatinib (Specialist drug)

How it works

It potently inhibits ALK (and ROS1) tyrosine kinases, including several resistance mutations, and has good central nervous system penetration to control brain metastases.

Prescribing in practice

• It frequently causes central nervous system effects including mood, cognitive, speech and psychotic changes, which should be monitored for and may require dose interruption or reduction.
• Marked hyperlipidaemia (raised cholesterol and triglycerides) is very common and often needs lipid-lowering therapy.
• It is a CYP3A substrate, so concomitant strong CYP3A inducers and inhibitors are contraindicated or avoided, and grapefruit should be excluded.

Monitoring

Monitor lipids, liver function and for new neurocognitive, mood or cardiac (AV conduction) effects, plus blood pressure, throughout treatment.

Counselling the patient

• Report changes in mood, memory, speech or behaviour to your team, as the dose may need adjusting.
• Avoid grapefruit and check all new medicines and supplements for interactions before starting them.
• Expect cholesterol monitoring and the possible need for a cholesterol-lowering tablet.

Evidence & guidelines

The CROWN trial established first-line efficacy in ALK-positive advanced non-small-cell lung cancer; use follows NICE and specialist guidance.