Lazertinib - Indications, Contraindications, and Side Effects

What Is Lazertinib?

Lazertinib is a medicine used to treat adults with advanced or metastatic non-small cell lung cancer, which is a common type of lung cancer. It is used when the cancer has certain EGFR gene changes. Before starting treatment, doctors perform an FDA-approved test to detect these mutations in a tumor or blood sample. Lazertinib is often given together with Amivantamab, a targeted antibody treatment, as the initial treatment. This medicine belongs to a group of drugs called kinase inhibitors. It works by blocking signals that promote cancer cell growth. It can be used alone or with other cancer medicines.

FDA Approval

Lazertinib was approved by the United States Food and Drug Administration (US FDA) on August 19, 2024.

How Does Lazertinib Work?

Lazertinib is a third-generation tyrosine kinase inhibitor. The drug is used to treat non-small cell lung cancer in patients with specific EGFR gene mutations. It targets the abnormal EGFR proteins in the cancer cells. These abnormal EGFR proteins help cancer cells grow and multiply. When these abnormal EGFR proteins are stopped from working, the cancer cells slow down or die. It can also cross the blood-brain barrier and help treat cancer cells in the brain. It causes less damage to normal cells because it targets only cancer cells.

FDA Approval Date

Lazertinib received its approval from the United States Food and Drug Administration in 2024.

Indications of Lazertinib

Lazertinib in combination with Amivantamab is used as a first-line therapy for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC). Treatment is initiated after an FDA-approved test confirms the presence of an EGFR exon 19 deletion or an exon 21 L858R substitution mutation in the tumor.

Contraindications of Lazertinib

Lazertinib is not recommended for pregnant and lactating women, children, or patients with severe hepatic or renal disorders.

Available Doses and Dose Forms

Lazertinib is available in 80 mg (milligrams) and 240 mg tablets. The recommended dose is 240 mg of Lazertinib with Amivantamab taken orally once a day until unacceptable toxicity or disease progression. Lazertinib tablets must be swallowed whole and not crushed, chewed, or split. It must be administered before Amivantamab when given on the same day.

Warnings and Precautions

• When the two medicines, i.e., Lazertinib and Amivantamab, are given together, it sometimes causes serious side effects. One side effect that might occur is blood clots in the veins. Blood clots might develop in the legs or lungs. To prevent blood clots in the veins, blood thinners may be given for the first few months.

• This combination of medicines might also cause lung side effects. Lung inflammation and lung irritation might be caused. Patients might be tested for cough, fever, and breathing difficulty. If the symptoms of lung inflammation and irritation occur, the medicines might be stopped.

• Eye side effects may also occur. Eye side effects might include eye pain, blurred vision, and redness of the eye. If any of the eye side effects occur, an eye doctor might be consulted. The dose might be stopped or lowered. Rash, itching, acne-like bumps, and dry skin may also be caused.

Adverse Effects of Lazertinib

Some of the adverse effects of Lazertinib include:

• Cough.

• Fever.

• Difficulty breathing.

• Redness and dryness of the skin.

• Severe rash.

• Itching.

• Raised acne-like bumps.

• Vision problems.

• Constipation.

• Muscle and joint pain.

• Tiredness.

• Reduced appetite.

• Nausea.

• Infusion-related reactions.

• Sores in the mouth.

• Swelling.

• Diarrhea.

For Patients

How Effective Is Lazertinib?

The drug works as a first-line treatment in the treatment of advanced non-small cell lung cancer with EGFR mutations. It is effective in treating cancer and is safe in the majority of adult patients. It can be used in patients with the T790M mutation and may help control cancer for a longer time. It can be used in patients with cancer whose cancer cells have spread to the brain.

How Should Lazertinib Be Taken?

Lazertinib must be taken exactly as prescribed by the doctor. It is usually recommended once daily, with or without food. Lazertinib tablets must be swallowed whole and not crushed, split, or chewed. It may be given in combination with other anti-cancer medicines. If given along with Amivantamab, Lazertinib must be taken at any time before receiving Amivantamab infusion.

What Are the Side Effects of Lazertinib?

Some of the side effects of Lazertinib include:

• Muscle and joint pain.

• Rash.

• Mouth sores.

• Swelling of hands and feet.

• Diarrhea.

• Tiredness.

• Bleeding.

• Constipation.

• Itchy skin.

• Decreased appetite.

• Nausea.

• Infected skin around the nail.

• Infusion-related reactions.

What Must the Patient Inform the Doctor About Before Taking Lazertinib?

Before taking Lazertinib, patients must inform their doctor of any lung or breathing problems or other medical conditions. Before starting treatment, patients must inform the doctor if they take vitamins or nutritional supplements, herbal medicines, over-the-counter (OTC) drugs, or other medications.

Women should inform their doctor if they are pregnant, planning to become pregnant, or breastfeeding before starting treatment with Lazertinib.

Missed Dose

If a dose of Lazertinib is missed, it should be taken within 12 hours; if this time has passed, the missed dose should be skipped and the next dose taken at the regular time. If vomiting occurs any time following the drug intake, the patient must take the next dose at its regularly scheduled time.

Overdose

In case of an overdose of Lazertinib or if serious side effects are observed, the healthcare specialist must be contacted immediately.

Storage

Lazertinib tablets must be stored in their original packaging at 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit), away from excess heat and moisture, and out of the reach of children.

For Doctors

Pharmacological Aspects of Lazertinib

• Mechanism of Action - Lazertinib is an epidermal growth factor receptor (EGFR) and a kinase inhibitor that inhibits EGFR exon 21 L858R substitution mutations and exon 19 deletions at lower concentrations than wild-type EGFR. Lazertinib exhibits anti-tumor activity, which is comparatively higher in combination with Amivantamab than in monotherapy.

• Pharmacodynamics - Lazertinib is an anticancer agent demonstrating anti-tumor activity in human NSCLC cells harboring EGFR exon 19 deletions or L858R mutations. In combination with Amivantamab, Lazertinib shows greater activity than the agent alone.

• Pharmacokinetics - After administering a single dose of once-daily Lazertinib, the maximum plasma concentration (Cmax) and area under the curve (AUC) increased proportionally, and the steady state was achieved by day 15.

  • Absorption - The drug usually reaches its peak blood concentration within 2 to 4 hours. Eating a high-fat meal does not significantly change its absorption compared with taking it on an empty stomach.

  • Distribution - About 99.2 percent of Lazertinib is bound to plasma proteins, and the mean apparent volume of distribution is approximately 2680 L (liters).

  • Metabolism - Lazertinib is mainly metabolized either by enzymatic via glutathione S-transferase by glutathione conjugation or non-enzymatic and CYP3A4.

  • Excretion - After a single oral dose of Lazertinib (radiolabeled) administration, approximately 86 percent of the dose was recovered in feces, and four percent was recovered in urine. The mean terminal half-life of Lazertinib is around 3.7 days, with the mean apparent clearance of 36.4 L/H (liters per hour).

Drug Interactions

• Some of the drugs that may interact with Lazertinib include:

• Acenocoumarol.

• Acalabrutinib.

• Abemaciclib.

• Abametapir.

• Afatinib.

• Ambroxol.

• Alpelisib.

• Albendazole.

• Alectinib.

• Allopurinol.

• Ciprofloxacin.

• Rifampin.

Specific Considerations

• Pregnancy: Lazertinib is not recommended for pregnant women, as it can harm the fetus.

• Lactation: Lazertinib must be avoided during breastfeeding, as there is no data to determine the potential for severe adverse reactions in breastfed infants or milk production.

• Pediatric Use: The safety and efficacy of Lazertinib have not been determined in children.

• Geriatric Use: No significant differences were observed in the safety or effectiveness of Lazertinib in patients aged 65 years or older with NSCLC compared with younger patients.

Conclusion:

Lazertinib is a targeted therapy used to treat certain types of advanced lung cancer. It works by blocking signals that allow cancer cells to grow and spread. While the medicine can be effective, it may also cause side effects, so regular medical checkups are important during treatment. Patients should take Lazertinib exactly as prescribed to help ensure the treatment is safe and works as intended. For more details, talk to our cancer specialist.