Selpercatinib – Highly Selective RET Kinase Inhibitor
Selpercatinib is a highly selective and potent oral inhibitor of the RET (Rearranged during Transfection) receptor tyrosine kinase. The drug represents a new generation of targeted therapy specifically developed to treat tumors driven by specific genetic alterations in the RET gene. Selpercatinib effectively blocks the activity of abnormal RET proteins that cause cancer cells to divide and survive uncontrollably, providing a pronounced antitumor response with minimal impact on other kinase types.
The mechanism of action of selpercatinib involves the direct inhibition of both wild-type RET isoforms and various mutant forms and fusion proteins. Genetic rearrangements and mutations of the RET gene are found in various cancers, including thyroid cancer and non-small cell lung cancer. The drug is capable of crossing the blood-brain barrier, making it effective in treating brain metastases. Due to its ultra-high selectivity, selpercatinib has significantly less effect on VEGFR2 receptors compared to previous generations of multikinase inhibitors, avoiding many severe vascular side effects. Use of the drug allows for long-term disease stabilization and a substantial reduction in tumor size in patients with confirmed RET-positive malignancies.
The drug is taken orally twice daily and requires prior genetic testing to confirm the presence of RET gene alterations.
Indications
Selpercatinib is indicated for adults and adolescents for the treatment of advanced or metastatic tumors with RET gene alterations:
- Non-Small Cell Lung Cancer (NSCLC): treatment of patients with RET gene fusions (RET fusion-positive).
- Medullary Thyroid Cancer (MTC): therapy for patients aged 12 years and older with a RET gene mutation who require systemic treatment.
- Other Thyroid Cancers: treatment of patients with RET-positive cancer that is resistant to radioactive iodine therapy.
- Solid Tumors: therapy for other types of malignant neoplasms with confirmed RET gene fusions when alternative treatment options are unavailable.
Dosage and administration
The dose of selpercatinib is selected individually based on the patient's body weight and therapy tolerability.
- Patients weighing less than 50 kg: the recommended dosage is 120 mg twice daily.
- Patients weighing 50 kg or more: the recommended dosage is 160 mg twice daily.
- Administration Method: capsules are taken orally every 12 hours, regardless of food intake. Capsules should be swallowed whole and not chewed.
- Adjustment for Side Effects: if toxicity develops, the dose is sequentially reduced to 120 mg, 80 mg, or 40 mg twice daily.
- Interaction with PPIs: when taking heartburn medications (proton pump inhibitors), selpercatinib should be taken strictly with a full meal.
