ROZLYTREK

What it is

Rozlytrek is a medicine containing entrectinib . It is supplied as hard capsules containing either 100 mg or 200 mg of entrectinib . Entrectinib is an antineoplastic agent and tyrosine kinase inhibitor . This medicinal product is subject to additional monitoring in Australia .

Approved indications

— Advanced non-small cell lung cancer (NSCLC) in adult patients whose tumours are ROS1-positive . — Solid tumours in adult and paediatric patients 12 years of age and older with NTRK gene fusion without a known acquired resistance mutation, metastatic or where surgical resection is likely to result in severe morbidity, and either progressed following treatment or have no satisfactory alternative therapy .

Dosing overview

The recommended dose of Rozlytrek for adults is 600 mg given orally, once daily . For paediatric patients, the recommended dose is based on body surface area . Rozlytrek can be taken with or without food, capsules should be swallowed whole, and capsules must not be opened or dissolved .

Key safety warnings

Congestive heart failure has been reported across clinical trials with Rozlytrek in patients with or without a history of cardiac disease and resolved upon treatment with diuretics and/or dose reduction or interruption of Rozlytrek . Left ventricular ejection fraction should be assessed prior to initiation of Rozlytrek in patients with symptoms or known risk factors for congestive heart failure . A broad spectrum of central nervous system adverse reactions were reported in clinical trials with Rozlytrek, including cognitive impairment, mood disorders, dizziness and sleep disturbances . Patients and caregivers should be advised of these risks, and patients should not drive or operate hazardous machinery if experiencing central nervous system adverse reactions . Rozlytrek increases the risk of fractures . Patients with signs or symptoms of fractures should be promptly evaluated; in paediatric patients some fractures occurred with no trauma . Hepatic transaminase elevation was frequently reported in entrectinib clinical trials, and liver function tests including ALT and AST should be monitored every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated . Hyperuricaemia was frequently reported in entrectinib clinical trials with 34% of cases requiring medical intervention to reduce serum urate; serum urate should be assessed prior to initiating Rozlytrek and periodically during treatment . QT interval prolongation was observed in patients treated with Rozlytrek in clinical trials; patients with congenital long QT syndrome, clinically significant bradyarrhythmias, severe or poorly controlled heart failure or taking medications associated with QT interval prolongation should be monitored, with QT interval and electrolytes assessed at baseline and periodically during treatment . Vision changes were reported in 21% of patients treated with Rozlytrek; for patients with new visual changes or changes that interfere with activities of daily living, treatment modification may be necessary .

Contraindications

Rozlytrek is contraindicated in patients with a known hypersensitivity to entrectinib or any of the excipients .

PBS listing

The 200 mg capsule formulation is listed on the PBS with one item under an authority required restriction, with an ex-manufacturer price of A$6771.89 .

Regulatory history

Rozlytrek 100 mg and 200 mg hard capsules were first registered on the ARTG on 2020-05-15 . The AusPAR approval date was 2020-05-14 . In March 2020, the PBAC recommended listing for locally advanced or metastatic ROS1-positive non-small cell lung cancer on a cost-minimisation basis compared with crizotinib . The NTRK fusion-positive solid tumour indication was approved via the provisional approval pathway based on objective response rate and duration of response in single-arm trials, with full registration depending on verification and description of clinical benefit in confirmatory trials .