RETEVMO

What it is

RETEVMO is selpercatinib, available as 40 mg and 80 mg immediate release hard capsules. Selpercatinib is an orally available, small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase. This medicinal product is subject to additional monitoring in Australia.

Approved indications

— Treatment of adult patients with locally advanced or metastatic RET fusion positive non-small cell lung cancer (NSCLC). — Treatment of adult and adolescent (12 years of age and older) patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy.

Dosing overview

The recommended dose of RETEVMO based on body weight is: less than 50 kg, 120 mg twice daily; 50 kg or greater, 160 mg twice daily. Treatment should be continued until disease progression or unacceptable toxicity. RETEVMO is for oral administration. The capsules should be swallowed whole and can be taken with or without food. Patients should take the doses at approximately the same time every day.

Key safety warnings

Interstitial lung disease (ILD) and/or pneumonitis, including severe and life-threatening disease, was reported in patients receiving selpercatinib. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis and treated as medically appropriate. Based on the severity of ILD/pneumonitis, selpercatinib may require dose interruption or discontinuation. Grade 3 or greater increased ALT and AST were reported in patients receiving selpercatinib. ALT and AST should be monitored prior to the start of selpercatinib therapy, every 2 weeks during the first 3 months of treatment, monthly for the next 3 months of treatment, and otherwise as clinically indicated. Based on the level of ALT or AST elevations, selpercatinib may require dose modification. Hypertension was reported in patients receiving selpercatinib. Patient blood pressure should be controlled before starting selpercatinib treatment, monitored during selpercatinib treatment and treated as needed with standard anti-hypertensive therapy. Based on the level of increased blood pressure, selpercatinib may require dose modification. Selpercatinib should be discontinued permanently if medically significant hypertension cannot be controlled with antihypertensive therapy. QT interval prolongation was reported in patients receiving selpercatinib. Selpercatinib should be used with caution in patients with congenital long QT syndrome or acquired long QT syndrome or other clinical conditions that predispose to arrhythmias. Patients should have a QTcF interval of ≤470 ms and serum electrolytes within normal range before starting selpercatinib treatment. Electrocardiograms and serum electrolytes should be monitored in all patients after 1 week of selpercatinib treatment, at least monthly for the first 6 months and otherwise as clinically indicated. Hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to initiating selpercatinib and during treatment. Hypersensitivity was reported in patients receiving selpercatinib with a majority of events observed in patients with NSCLC previously treated with anti-PD-1/PD-L1 immunotherapy. Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or elevated aminotransferases. Suspend selpercatinib if hypersensitivity occurs and begin steroid treatment. Serious including fatal haemorrhagic events were reported in patients receiving selpercatinib. Permanently discontinue selpercatinib in patients with severe or life-threatening haemorrhage. Selpercatinib can cause hypothyroidism. Monitor thyroid function before treatment with RETEVMO and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated, however patients could have an insufficient response to substitution with levothyroxine (T4) as selpercatinib may inhibit the conversion of levothyroxine to triiodothyronine (T3) and supplementation with liothyronine may be needed.

Contraindications

RETEVMO is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

PBS listing

RETEVMO 80 mg capsules are listed on the PBS with streamlined authority required restriction at an ex-manufacturer price of A$3950.00. RETEVMO 40 mg capsules are listed on the PBS with streamlined authority required restriction at an ex-manufacturer price of A$1975.00.

Regulatory history

RETEVMO received provisional approval on 2023-06-27 for the treatment of adult patients with locally advanced or metastatic RET fusion positive non-small cell lung cancer (NSCLC). This provisional approval is based on objective response rate and duration of response from a single arm study, with continued approval dependent on verification in a confirmatory trial. In July 2023, the PBAC did not recommend RETEVMO for non-small cell lung cancer, but in July 2024, the PBAC recommended RETEVMO for advanced or metastatic, rearranged during transfection (RET) fusion-positive NSCLC.