Adverse Reactions of Repotrectinib

Adverse Reactions of Repotrectinib

In the TRIDENT-1 study, among 426 patients treated with repotrectinib, up to 77% experienced central nervous system adverse reactions, including dizziness, ataxia, and cognitive impairment, with 4.5% experiencing grade 3 or 4 serious events. Dizziness (including vertigo) was the most common CNS event, occurring in 65% of patients. Ataxia (gait disturbance, balance disorder) occurred in 28% of patients. Cognitive impairment (memory impairment, attention deficit, confusion) occurred in 25% of patients. Additionally, mood disorder (6%) and sleep disorder (18%) were reported. The incidence of adverse reactions was similar regardless of the presence of CNS metastases. Patients experiencing such reactions are advised to avoid driving or operating machinery, and physicians should consider dose interruption, reduction, or permanent discontinuation based on severity.

Interstitial Lung Disease/Pneumonitis with Repotrectinib

In clinical trials, the overall incidence of interstitial lung disease or pneumonitis was 3.1%, with 1.2% of patients experiencing grade 3 events. These events included pneumonitis (2.8%) and interstitial lung disease (0.2%). Physicians should closely monitor patients for new or worsening pulmonary symptoms, such as dyspnea, cough, fever, etc. For suspected interstitial lung disease or pneumonitis, repotrectinib should be immediately interrupted; once confirmed, the drug must be permanently discontinued. Early identification and intervention are key to reducing the risk of this serious adverse reaction.

Hepatotoxicity of Repotrectinib

Treatment with repotrectinib can cause elevation of liver enzymes. Alanine aminotransferase elevation occurred in 38% of patients, and aspartate aminotransferase elevation occurred in 41%, with grade 3 or 4 severe elevations accounting for 3.3% and 2.9%, respectively. During the first month of treatment, liver function tests including alanine aminotransferase, aspartate aminotransferase, and bilirubin are recommended every 2 weeks, then monthly thereafter, with increased frequency as clinically indicated. Based on the severity of hepatotoxicity, physicians should decide on dose interruption, reduction, or permanent discontinuation. Enhanced supportive care should be provided for patients with clinical signs of liver injury.