Lorlatinib is a targeted therapy medication used in oncology, known by the brand name Lorbrena. Unlike traditional chemotherapy that affects all rapidly dividing cells, targeted therapies like lorlatinib are designed to interfere with specific proteins involved in the growth and spread of tumors. This approach represents a more precise method in the treatment of certain cancers.
Medical Uses of Lorlatinib
Lorlatinib is prescribed for a particular form of lung cancer known as anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). NSCLC is the most common type of lung cancer, and “ALK-positive” signifies that the cancer cells have a specific genetic alteration that produces an abnormal protein, fueling cancer growth. The term “metastatic” means the cancer has spread from the primary site in the lung to other parts of the body.
This medication is often used as an initial treatment for this condition. Clinical studies have shown it to be superior to older drugs in slowing the progression of the disease. For instance, in one major clinical trial, 60% of participants receiving lorlatinib were alive after five years without their disease worsening, compared to only 8% of those receiving an earlier medication called crizotinib.
A significant application for lorlatinib is in treating patients whose cancer has become resistant to other ALK-inhibitor drugs. It is a third-generation inhibitor, designed specifically to overcome mutations that tumors can develop, which make previous generations of these drugs ineffective. Because ALK-positive lung cancer has a high tendency to spread to the brain, lorlatinib is effective in treating existing brain metastases and helping to prevent new ones from forming.
Mechanism of Action
Lorlatinib works by targeting the underlying genetic cause of the cancer’s growth. In ALK-positive NSCLC, a gene fusion creates an abnormal ALK protein that functions as a tyrosine kinase. This protein acts like a switch that is permanently stuck in the “on” position, sending signals that tell cancer cells to grow and divide. Lorlatinib functions as a tyrosine kinase inhibitor (TKI) designed to interrupt this signaling process.
The drug’s molecular structure allows it to fit precisely into the ATP-binding pocket of the ALK protein. This action is analogous to a key breaking off in a lock, which blocks the lock from being used. By binding to this site, lorlatinib prevents the ALK protein from using energy to send its growth signals, a process known as phosphorylation.
A distinguishing feature of lorlatinib is its ability to cross the blood-brain barrier. This physiological barrier is a network of blood vessels and tissue that protects the brain from harmful substances, but it can also prevent many cancer drugs from reaching tumors in the central nervous system. Lorlatinib was designed to be brain-penetrant, allowing it to reach and act on cancer cells that have spread to the brain.
Common Side Effects and Management
Patients taking lorlatinib may experience a range of manageable side effects. Among the most frequently reported are changes in blood lipid levels, specifically high cholesterol (hypercholesterolemia) and high triglycerides (hypertriglyceridemia). These metabolic changes appear early in treatment and management involves lipid-lowering medications and regular monitoring through blood tests.
Other common side effects include:
- Edema, which is swelling caused by excess fluid in the hands, feet, and ankles.
- Peripheral neuropathy, characterized by numbness, tingling, or pain in the hands and feet.
- Changes in cognitive function, such as difficulty with memory or attention.
- Alterations in mood or speech.
These effects are mild and often reversible with a dose adjustment.
While many side effects are mild to moderate, less common but more serious events require immediate medical attention. Lung problems, such as pneumonitis, can develop, presenting with symptoms like a new or worsening cough or difficulty breathing. Liver function can also be affected, indicated by symptoms like yellowing of the skin or eyes, dark urine, or pain in the upper right abdomen. Patients should report any new or worsening symptoms to their healthcare team promptly.
Administration and Important Precautions
Lorlatinib is an oral medication administered as a tablet, taken once daily at approximately the same time each day, with or without food. If a patient misses a dose, they should take it as soon as they remember, unless the next scheduled dose is less than four hours away. In that case, the missed dose should be skipped to avoid taking a double dose.
Certain substances must be avoided during treatment as they can interfere with how the body processes the drug. Grapefruit and grapefruit juice can significantly increase the concentration of lorlatinib in the blood, leading to a higher risk of side effects. This is because grapefruit inhibits CYP3A4, an enzyme responsible for breaking down the drug. Conversely, the herbal supplement St. John’s wort can decrease the drug’s effectiveness.
Before starting treatment, patients should inform their doctor of all medications they are taking, including prescriptions, over-the-counter drugs, and herbal products. Regular monitoring is a part of the treatment plan. This includes blood tests to check cholesterol and triglyceride levels, as well as tests to monitor liver function. Blood pressure should also be checked regularly.