STIVARGA

What it is

Stivarga contains 40 mg regorafenib per film-coated tablet. Regorafenib is an oral anti-tumour agent that potently blocks multiple protein kinases, including kinases involved in tumour angiogenesis, oncogenesis, metastasis and tumour immunity.

Approved indications

— Metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild type, an anti-EGFR therapy. — Unresectable or metastatic gastrointestinal stromal tumours in patients who progressed on or are intolerant to prior treatment with imatinib and sunitinib. — Hepatocellular carcinoma in patients previously treated with sorafenib.

Dosing overview

The standard dosing regimen is four Stivarga 40 mg tablets daily (160 mg total) taken at the same time each day for three weeks on therapy followed by one week off therapy to comprise a cycle of four weeks. Tablets should be swallowed whole with water after a low-fat meal containing less than 30 per cent fat. The lowest recommended daily dose is 80 mg and the maximum daily dose is 160 mg.

Key safety warnings

Rare cases of fatal hepatotoxicity have been observed in clinical trials and in the post-marketing setting, including in the absence of hepatic metastases. Liver function tests should be performed before initiation of treatment and monitored closely at least every two weeks during the first two months of treatment, then periodically at least monthly and as clinically indicated. Stivarga has been associated with an increased incidence of haemorrhagic events, some of which were fatal, involving the respiratory, gastrointestinal, or genitourinary tracts. Gastrointestinal perforation and fistulae have been reported in patients treated with Stivarga. Stivarga has been associated with an increased incidence of myocardial ischaemia and infarction, and patients with a history of ischaemic heart disease should be monitored for clinical signs and symptoms. Hyperammonemic encephalopathy has been observed with Stivarga, including fatal cases, and ammonia level should be measured in patients who develop unexplained lethargy or changes in mental status. Stivarga has been associated with an increased incidence of arterial hypertension, with onset during the first cycle of treatment in most patients. Blood pressure must be adequately controlled before initiation, and should be monitored weekly for the first six weeks of treatment and then every cycle. Hand-foot skin reaction and rash represent the most frequently observed dermatological adverse reactions, and measures for prevention include control of calluses and use of shoe cushions and gloves.

Contraindications

Stivarga is contraindicated in patients with hypersensitivity to any of the ingredients contained in the product.

PBS listing

No sources provide information regarding PBS listing details for Stivarga.

Regulatory history

Stivarga regorafenib 40 mg tablet was first listed on the ARTG on 29 November 2013. An Australian Public Assessment Report was issued on 18 March 2015 for the indication of unresectable or metastatic gastrointestinal stromal tumours in patients who progressed on or are intolerant to prior treatment with imatinib and sunitinib. In November 2021, the PBAC recommended against listing for colorectal cancer.