Lazcluze (Lazertinib) - What are the precautions for lazertinib?

In the clinical study of Lazcluze (Lazertinib) - lazertinib combined with amivantamab (Evantumumab ) in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), warnings and precautions such as venous thromboembolic events, interstitial lung disease/pneumonitis, skin adverse reactions, eye toxicity, embryo-fetal toxicity, etc. occurred. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Venous thromboembolic events (VTE):Including deep vein thrombosis (DVT) and pulmonary embolism (PE). Most of these events occur in the first four months of treatment. Prophylactic anticoagulation was administered during the first four months of treatment. Vitamin K antagonists are not recommended. Monitor for signs and symptoms of VTE and initiate appropriate medical treatment.

Discontinue Lazcluze and amivantamab based on severity Once anticoagulant therapy is initiated, Lazcluze and amivantamab may be resumed at the same dose level at the discretion of the healthcare provider. In case of recurrence of VTE after anticoagulation therapy, permanently discontinue amivantamab. The healthcare provider may continue treatment with the same dose level of Lazcluze at the discretion of the healthcare provider.

2. Interstitial lung disease (ILD)/pneumonia: Monitor patients for new or worsening ILD/pneumonia symptoms (such as dyspnea, cough, fever); for patients with suspected ILD/pneumonia, Lazcluze and amivantamab should be discontinued immediately. If ILD/pneumonitis is confirmed, Lazcluze and amivantamab should be discontinued permanently.

3. Adverse skin reactions: May cause severe rashes, including acneiform dermatitis, itching and dry skin. When initiating treatment with Lazcluze in combination with amivantamab, an alcohol-free (e.g., isopropyl alcohol, ethanol-free) moisturizer should be used to reduce the risk of adverse skin reactions. Instruct patients to limit sun exposure during and for 2 months after treatment with Lazcluze plus amivantamab. Patients are advised to wear protective clothing and use broad-spectrum UVA/UVB sunscreen.

Consider preventive measures (such as oral antibiotics) to reduce the risk of adverse skin reactions. If skin reaction occurs, use topical corticosteroids and topical and/or oral antibiotics. For grade 3 reactions, administer oral steroids and consider dermatologic consultation. Refer patients who develop a severe rash, atypical appearance or distribution, or no improvement within two weeks to a physician immediately.

4. Eye toxicity: including keratitis. Refer patients who develop new or worsening eye symptoms to an ophthalmologist immediately.

5. Embryo-Fetal Toxicity: Based on the results of animal studies and its mechanism of action, Lazcluze taken by pregnant women may cause harm to the fetus. In animal reproduction studies, oral administration of lacetinib to pregnant animals during the organogenesis period resulted in reduced embryo-fetal survival and fetal weight in rats and malformation rates in rabbits that were 4 times and 0.5 times the recommended human dose of 240 mg/day, respectively, based on AUC.

Inform pregnant women and women of reproductive potential of the potential risks to the fetus. It is recommended that females of reproductive potential use effective contraception during treatment and for 3 weeks after the last dose; male patients of female partners of reproductive potential are advised to use effective contraception during treatment and for 3 weeks after the last dose.