In May 2020, the U.S. Food and Drug Administration gave accelerated approval for selpercatinib (Retevmo®) to treat RET-altered non-small cell lung cancer (NSCLC) or thyroid cancer based on overall response rate and duration of response. Selpercatinib fights cancer by impeding RET protein activity. The determining clinical trial results demonstrated that it reduced tumor size in more than 50% of patients and was associated with fewer adverse reactions than other drugs that block the RET protein.
Targeted therapy; kinase inhibitor
Selpercatinib is indicated for adult patients with metastatic RET fusion-positive NSCLC. It’s also indicated for adult and pediatric patients 12 years of age and older with advanced or metastatic RET-altered medullary thyroid cancer who require systemic therapy or fusion-positive thyroid cancer who require systemic therapy and who are refractory to radioactive iodine.
Dosage and Administration
Patients weighing less than 110 pounds (50 kg) should receive 120 mg orally twice daily; those more than 110 pounds receive 160 mg orally twice daily. Selpercatinib is a pill and can be taken with or without food. Take the pill at the same time each day. If coadministered with a proton pump inhibitor, take with food. Take 2 hours before or 10 hours after administration of an H2-receptor antagonist. Take 2 hours before or 2 hours after administration of a locally acting antacid.
More than 25% of patients experience elevated liver enzymes (aspartate aminotransferase [AST] or increased alanine aminotransferase [ALT]), increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation. A total of 15% of patients have QTc prolongation, 2.3% have hemorrhagic events, and 4.3% have hypersensitivity reaction.
Monitor ALT and AST prior to starting therapy, every two weeks for the first three months, then monthly or as clinically indicated. Ensure patients’ blood pressure is stabilized prior to starting therapy. Monitor blood pressure one week after starting therapy and at least monthly.
Monitor electrolytes and thyroid-stimulating hormone prior to starting treatment and periodically throughout treatment if administered concomitantly with a moderate or strong CYP3A inhibitor or other drugs known to prolong the QTc interval.
Monitor for hypersensitivity reactions. If one occurs, withhold selpercatinib and start corticosteroids.
Stop therapy at least one week prior to surgery and withhold two weeks following surgery because of impaired wound healing.
Complete a medication reconciliation to look for possible drug interactions, including acid-reducing agents, strong and moderate CYP3A inhibitors, strong and moderate CYP3A inducers, and CYP2C8 and CYP3A substrates. If coadministration cannot be avoided, adjust dose as recommended in the package insert.
Review dosing, administration instructions, symptoms, and when to contact the healthcare team. Advise females of reproductive potential of the possible risk to the fetus and to use effective contraception. Women should not breastfeed when taking selpercatinib. If patients miss a dose, do not take it unless it is more than six hours until next scheduled dose. A patient education sheet is available at oralchemoedsheets.com/sheets/Selpercatinib_Patient_Education.pdf.
No overall differences in safety or effectiveness were seen in clinical trials between younger and older patients. Consider comorbidities in risk assessment for older adults (e.g., hypertension, QTc prolongation, hepatotoxicity, concurrent medications)
Selpercatinib can cause embryo-fetal toxicity.