Lorlatinib is a targeted therapy medication used in the treatment of certain cancers. This drug specifically addresses tumors with particular genetic changes, marking a shift towards more personalized approaches in cancer care. It focuses on disrupting specific pathways that drive cancer growth, offering a distinct treatment strategy.
What Lorlatinib Treats
Lorlatinib is primarily used to treat non-small cell lung cancer (NSCLC) that possesses specific genetic alterations. These alterations involve the anaplastic lymphoma kinase (ALK) gene or the c-ros oncogene 1 (ROS1) gene. When these genes undergo chromosomal rearrangements, they can create abnormal fusion proteins, which then promote uncontrolled cell growth and survival, leading to cancer.
This medication is particularly relevant for patients with ALK-positive NSCLC, especially those whose disease has progressed despite treatment with other ALK inhibitors. ALK-positive NSCLC has been treated with various ALK tyrosine kinase inhibitors (TKIs), but resistance often develops. Lorlatinib offers an option for patients who have progressed on earlier generations of these inhibitors, including crizotinib, alectinib, or ceritinib.
The drug also treats ROS1-positive NSCLC, which accounts for 1% to 2% of NSCLC cases. Lorlatinib is considered a treatment option for metastatic ROS1-positive NSCLC in patients who have previously received crizotinib, ceritinib, or entrectinib.
Lorlatinib can address cancer spread to the brain. Patients with ALK or ROS1-positive NSCLC frequently develop brain metastases.
How Lorlatinib Works
Lorlatinib functions as a tyrosine kinase inhibitor (TKI), specifically targeting abnormal ALK and ROS1 fusion proteins. These fusion proteins act as enzymes that continuously signal cellular pathways, driving the uncontrolled division and survival of cancer cells. In healthy cells, ALK proteins are only activated when other molecules bind to them, but in ALK-positive NSCLC, the fused ALK proteins can switch themselves on independently.
The drug works by binding to a specific area on these aberrant ALK and ROS1 tyrosine kinases, known as the ATP-binding pocket. This binding action inhibits their activity, thereby halting the phosphorylation process that is crucial for activating downstream signaling cascades. By disrupting these pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways, lorlatinib effectively slows or stops the growth of cancer cells and can lead to their programmed cell death.
Lorlatinib can penetrate the central nervous system. This property is particularly beneficial because ALK and ROS1-positive NSCLC often spreads to the brain. By reaching these areas, lorlatinib can treat existing brain metastases and potentially help prevent new ones from forming. The drug’s structure also allows it to remain effective against many ALK mutations that cause resistance to earlier ALK inhibitors, providing a treatment option for patients who have developed such resistance.
Managing Side Effects
Lorlatinib treatment can lead to various side effects. Common side effects include elevated cholesterol and triglyceride levels, swelling in the limbs, and peripheral neuropathy, which involves numbness or tingling in the hands and feet. Other frequently reported effects include cognitive changes like forgetfulness or confusion, fatigue, and high blood pressure.
Hyperlipidemia, or high levels of cholesterol and triglycerides, is a common side effect. This condition is managed with lipid-lowering medications, and many patients may require one or more such agents. Regular monitoring of blood lipid levels is important throughout treatment.
Swelling, known as edema, can occur. Peripheral neuropathy can also make fine motor tasks difficult. Central nervous system (CNS) effects, such as mood changes, cognitive issues, or speech difficulties, are distinct to lorlatinib compared to other ALK-TKIs. These side effects can be managed through dose adjustments or standard supportive care, with permanent discontinuation of the drug being uncommon.
Key Considerations for Treatment
Lorlatinib is administered as an oral tablet, taken once daily with or without food. Consistent dosing at the same time each day is important for maintaining its effectiveness. If a dose is missed and it is less than four hours until the next scheduled dose, the missed dose should be skipped; a double dose should not be taken.
Regular monitoring is a standard part of lorlatinib therapy to manage potential side effects and ensure treatment effectiveness. Blood tests are performed to check cholesterol and triglyceride levels, and blood pressure is also monitored. Neurological assessments are conducted to watch for any cognitive or mood changes.
Patients should be aware of potential drug interactions when taking lorlatinib. It is advised to avoid grapefruit and grapefruit juice, as they can increase the drug’s levels and the risk of side effects. Certain other medications can also interact with lorlatinib, potentially altering its effectiveness or increasing toxicity. It is important to inform healthcare providers about all other medications, including over-the-counter drugs and supplements, to avoid adverse interactions.
The goal of treatment with lorlatinib is disease control, and patients continue the medication for as long as it remains effective and side effects are manageable. Dose adjustments, including interruptions or reductions, may be implemented by the healthcare provider to help manage side effects. For instance, if severe hyperlipidemia occurs, the drug may be temporarily withheld until levels improve before resuming at the same or a reduced dose.