Zongertinib is a kinase inhibitor targeting activating mutations in the tyrosine kinase domain of HER2 (ERBB2). It is indicated for the treatment of unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) that has progressed following systemic therapy. Despite its significant efficacy, vigilance regarding potential side effects and precautions is required during administration.
What Are the Side Effects of Zongertinib?
Gastrointestinal Reactions
Diarrhea (53%): Most cases are mild, but caution is needed to prevent dehydration caused by persistent diarrhea.
Nausea (21%), 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 That Require Vigilance
Hepatotoxicity
Manifestations: Elevated ALT/AST (35%/31%), elevated bilirubin (20%); severe cases may lead to liver failure (0.4%).
Monitoring and Management: Monitor liver function before initiation of treatment and every 2 weeks for the first 12 weeks after treatment starts, then monthly thereafter.
For grade 3 or higher hepatotoxicity, interrupt treatment; upon recovery, reduce the dose or discontinue the drug 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 starting treatment and recheck it regularly during treatment.
Interrupt treatment if LVEF decreases by 10–19%; reduce the dose or discontinue the drug permanently if LVEF decreases by ≥20%.
Interstitial Lung Disease (ILD)/Pneumonitis
Manifestations: Dyspnea, cough, fever (incidence 1.2%); may be life-threatening.
Management: Once diagnosed, adjust the dose or discontinue the drug 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 potential 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): Concomitant use should be avoided; if unavoidable, the dose of zongertinib needs to be increased (e.g., from 120 mg to 240 mg).
BCRP substrates (e.g., rosuvastatin): Concomitant use may increase the plasma concentration of the latter; monitor for adverse reactions.
Administration 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.
