Zongertinib is a kinase inhibitor that targets activating mutations in the tyrosine kinase domain of HER2 (ERBB2). It is used for the treatment of unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) following systemic therapy. Despite its significant efficacy, potential side effects and precautions must be closely monitored during medication use.

What Are the Side Effects of Zongertinib?

Gastrointestinal Reactions

Diarrhea (53%): Most cases are mild, but caution is needed as persistent diarrhea may lead to dehydration.

Nausea (21%) and vomiting (15%).

Skin Reactions

Rash (27%): May present as erythema or pruritus.

Nail disorders (19%): Such as paronychia or nail loss.

Systemic Symptoms

Fatigue (22%).

Musculoskeletal pain (24%).

Abnormal Laboratory Indicators

Lymphopenia (52%).

Elevated ALT/AST (39%/33%).

Hypokalemia (20%).

Severe Side Effects of Zongertinib Requiring Vigilance

Hepatotoxicity

Manifestations: Elevated ALT/AST (35%/31%), elevated bilirubin (20%); in severe cases, it may lead to liver failure (0.4%).

Monitoring and Management: Monitor liver function before treatment and every 2 weeks for the first 12 weeks after starting treatment, then monthly thereafter.

Intervention: If Grade 3 or higher hepatotoxicity occurs, interrupt treatment; after recovery, resume at a reduced dose or discontinue permanently.

Left Ventricular Dysfunction

Risk: 6% of patients experience a decrease in left ventricular ejection fraction (LVEF), of which 1.9% are Grade 3.

Monitoring: Evaluate LVEF before treatment and recheck it regularly during treatment.

Intervention: Suspend treatment if LVEF decreases by 10-19%; if the decrease is ≥20%, reduce the dose or discontinue permanently.

Interstitial Lung Disease (ILD)/Pneumonitis

Manifestations: Dyspnea, cough, fever (incidence: 1.2%); may be life-threatening.

Management: Once diagnosed, adjust the dose or discontinue treatment permanently based on the severity.

Embryo-Fetal Toxicity

Risk: Animal studies have shown that zongertinib can cause fetal malformations; it is contraindicated in pregnant women.

Recommendation: Patients of childbearing age must use effective contraceptive measures during treatment and for 2 weeks after discontinuing the drug.

Precautions for Zongertinib Administration

Drug Interactions

Strong CYP3A Inducers (e.g., carbamazepine): Avoid concurrent use; if unavoidable, increase the dose of zongertinib (e.g., from 120mg to 240mg).

BCRP Substrates (e.g., rosuvastatin): Concurrent use may increase the plasma concentration of the latter; monitor for adverse reactions.

Medication Use in Special Populations

Lactating Women: Breastfeeding is prohibited during treatment and for 2 weeks after discontinuing the drug.

Elderly Patients: No dose adjustment is required, but close monitoring of liver function and cardiac indicators is necessary.