Oncology Overview: Selpercatinib in the Treatment of Medullary Thyroid Cancer

Selpercatinib (Retevmo, Loxo Oncology) is FDA-approved to treat 3 types of tumors—metastatic RET fusion-positive non-small cell lung cancer, advanced medullary thyroid cancer (MTC) or MTC that has spread, and advanced RET fusion-positive thyroid cancer.

Introduction

In May 2020, the FDA approved selpercatinib, 40 mg and 80 mg capsules (Retevmo, Loxo Oncology), to treat 3 types of tumors—non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and other types of thyroid cancers—in patients whose tumors have an alteration in a specific gene.

The drug is indicated for metastatic RET fusion-positive NSCLC, advanced MTC or MTC that has spread, in patients aged 12 years and older who require systemic therapy, and advanced RET fusion-positive thyroid cancer in patients aged 12 years and older that requires systemic therapy that has stopped responding to radioactive iodine therapy or is not appropriate for radioactive iodine therapy.


In the indication for the treatment of advanced or metastatic RET-mutant MTC, selpercatinib was approved for adult and pediatric patients 12 years of age and older.1,2 Medullary thyroid cancer is a tumor of the parafollicular or C cells in the thyroid gland.

In a study of 143 patients with advanced or metastatic RET-mutant MTC, 55 patients had previously undergone chemotherapy with other approved agents for MTC and 88 patients had not received prior treatment. Complete or partial shrinkage of the tumor was experienced in 69% of the previously treated group, with 76% lasting more than 6 months. In the treatment-naïve group, 73% experienced complete or partial shrinkage of their tumors, with 61% lasting greater than 6 months.2-4

Mechanism of Action2
Selpercatinib is a kinase inhibitor that inhibits wild-type RET, multiple other mutated RET isoforms, VEGFR1, and VEGFR3. Selpercatinib has also been shown to inhibit FGFR 1, 2, and 3 at clinically achievable higher concentrations.

Dosage and Administration1,2
Selpercatinib can be taken with or without food, but patients should avoid co-administering selpercatinib with a proton pump inhibitor. Capsules should be swallowed whole. Do not crush or chew.


Selpercatinib is dosed based on body weight.

  • For patients weighing less than 50 kg, 120 mg every 12 hours.
  • Patients weighing 50 kg or more, 160 mg every 12 hours.
  • Dose should be reduced in those patients with severe hepatic impairment.


Adverse Events (AEs)1,2
The most common AEs in patients taking selpercatinib were dry mouth, hypertension, fatigue, diarrhea, constipation, rash, and edema.

Common laboratory abnormalities include elevated AST/ALT, elevated glucose, elevated creatinine, elevated alkaline phosphatase, decreased albumin, decreased calcium, decreased leukocytes, decreased sodium and decreased platelet count.

Warnings and Precautions1,2

Selpercatinib caused hypertension in approximately 35% of patients. Health care providers should properly control patients’ blood pressure before starting selpercatinib. Blood pressure should be monitored after 1 week of starting therapy and at least monthly thereafter.

Selpercatinib was shown to cause concentration-dependent QT interval prolongation. Health care providers should monitor those patients most at risk of developing QTc prolongation. Potassium, magnesium, and calcium levels should be corrected before starting selpercatinib.

Due to the risk of serious hepatic AEs, health care providers should monitor their patient’s AST and ALT prior to beginning selpercatinib, every 2 weeks during the first 3 months of use, and then monthly thereafter.

Health care providers should monitor patients for signs of hypersensitivity to selpercatinib. Should hypersensitivity occur, selpercatinib should be withheld and corticosteroids should be initiated.

Once hypersensitivity event has resolved, selpercatinib can be resumed at a reduced dose and increased each week as tolerated. Should hypersensitivity occur a second time, selpercatinib should be permanently discontinued.

VEGF inhibitors are known to impair wound healing to various degrees, therefore patients taking selpercatinib should avoid taking the medication for at least 7 days prior to surgery. Selpercatinib should be held for at least 2 weeks after surgery and until the wound is adequately healed.

Rare cases of hemorrhagic events have also been shown with selpercatinib, including 3 patient fatalities. Selpercatinib should be permanently discontinued in patients exhibiting signs of severe hemorrhage.


Pregnancy and Lactation1,3
There are currently no available data on selpercatinib use in pregnant women to appropriately informdrug associated risk. When studied in pregnant rats, selpercatinib showed embryolethality and malformations at exposure levels that were approximately equal to those of human exposure at the dose of 160 mg twice daily.

Patients are advised not to breastfeed while taking selpercatinib as there are no data regarding the presence of the medication or its metabolites in human milk. Women should wait 1 week after their last dose to begin breastfeeding.

About the Author

Connor Walker, PharmD, is a clinical pharmacist at Yale New Haven Health

References


1. Drug Trial Snapshots: Retevmo. U.S. Food and Drug Administration. Accessed May 18, 2022. https://www.fda.gov/drugs/development-approval-process-drugs/drug-trials-snapshots-retevmo

2. Retevmo Prescribing information. January 2021. Accessed May 18, 2022
https://uspl.lilly.com/retevmo/retevmo.html#pi

3. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-lung-and-thyroid-cancers-certain-genetic-mutation-or-fusion

4. https://www.retevmo.com/hcp