Pralsetinib (Gavreto) is a targeted therapy for RET fusion-positive tumors. While delivering therapeutic benefits to patients, it is also associated with potential risks that cannot be ignored.
Adverse Reactions of Pralsetinib (Gavreto)
General Reactions
Fatigue: More than 40% of patients experience fatigue or asthenia.
Fever: Some patients may develop fever.
Edema: Localized or generalized swelling of the body, such as edema of the face, eyelids or extremities.
Gastrointestinal Reactions
Constipation: With a relatively high incidence, it is one of the main gastrointestinal adverse reactions.
Diarrhea: Some patients may have diarrhea, and a small number of cases may be severe.
Cardiovascular Reactions
Hypertension: Elevated blood pressure is an important and common adverse reaction of pralsetinib, requiring regular monitoring and management.
Severe Adverse Reactions of Pralsetinib (Gavreto)
Interstitial Lung Disease/Pneumonitis
Incidence: Occurs in approximately 12% of patients, among whom some cases are severe grade 3–4 reactions, and a very small number may be fatal.
Symptom Identification: New or worsening dyspnea, cough, and fever.
Management Measures: Patients should seek immediate medical attention and suspend medication once relevant symptoms appear. Physicians will decide whether to permanently discontinue the drug based on the severity of the reaction. For grade 1–2 reactions, the dosage should be reduced before resuming treatment after symptom resolution.
Hypertension
Pralsetinib may induce hypertension or exacerbate pre-existing hypertension.
Monitoring Requirements: Blood pressure must be well-controlled prior to the initiation of treatment. Monitor blood pressure during the first week of treatment, then at least once a month thereafter, and as clinically indicated.
Management Principles: In case of uncontrollable grade 3 hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg), treatment should be suspended and resumed at a reduced dose after blood pressure is controlled. Grade 4 hypertension (life-threatening) requires permanent discontinuation of the drug.
Hepatotoxicity
Pralsetinib may cause elevated liver enzymes and liver injury.
Monitoring Requirements: Measure alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels before treatment, every two weeks during the first three months of treatment, then monthly thereafter, and as clinically indicated.
Management Principles: Depending on the severity of elevated liver enzymes, treatment suspension, dosage reduction or permanent drug discontinuation may be required.
Precautions for Pralsetinib (Gavreto) Administration
Patient Selection and Dosage & Administration
Population Indications: This drug must be administered to patients with lung cancer or thyroid cancer confirmed to have RET gene fusion by an FDA-approved testing method.
Recommended Dosage: The recommended dose for adults and pediatric patients aged 12 years and older is 400 mg orally once daily, on an empty stomach (no food for at least 2 hours before dosing and at least 1 hour after dosing).
Missed Dose Management: If a dose is missed, take it as soon as possible on the same day and resume the normal dosing schedule the next day. Do not take an extra dose if vomiting occurs after administration.
Management of Drug Interactions
Concomitant Use with Inhibitors: Avoid co-administration with strong or moderate CYP3A inhibitors and/or P-glycoprotein inhibitors. If co-administration is unavoidable, the dosage of pralsetinib must be reduced in accordance with guidelines.
Concomitant Use with Inducers: Avoid co-administration with strong or moderate CYP3A inducers. If co-administration is unavoidable, the dosage of pralsetinib needs to be increased in accordance with guidelines.
Disclosure to Healthcare Providers: Patients must inform their physicians of all medications they are taking, including prescription drugs, over-the-counter drugs, vitamins and herbal products.
