CYRAMZA

What it is

Cyramza contains ramucirumab , a human IgG1 monoclonal antibody produced in murine cells by recombinant DNA technology . Ramucirumab is a human receptor-targeted antibody that specifically binds VEGF Receptor 2 and blocks binding of VEGF-A, VEGF-C, and VEGF-D , thereby inhibiting angiogenesis. Cyramza is available as a concentrate in 10 mL or 50 mL single-use vials containing either 100 mg ramucirumab in 10 mL (10 mg/mL) or 500 mg ramucirumab in 50 mL (10 mg/mL) . It is administered as an intravenous infusion .

Approved indications

— Advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum and fluoropyrimidine chemotherapy, in combination with paclitaxel . — Advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum or fluoropyrimidine chemotherapy when treatment in combination with paclitaxel is not appropriate, as monotherapy .

Dosing overview

Premedication is recommended with a histamine H1 antagonist (for example promethazine) intravenously prior to administration of ramucirumab .

Key safety warnings

Serious, sometimes fatal, arterial thromboembolic events including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischaemia have been reported in clinical trials . Ramucirumab must be permanently discontinued in patients who experience a severe arterial thromboembolic event . An increased incidence of severe hypertension was observed in clinical trials . Patients with uncontrolled hypertension were excluded from clinical trials and ramucirumab should not be commenced until their hypertension is controlled, with blood pressure monitored regularly . Severe gastrointestinal haemorrhage including fatal events were reported in patients with gastric adenocarcinoma treated with ramucirumab in combination with paclitaxel . Ramucirumab should be permanently discontinued in patients who experience Grade 3 or 4 bleeding . Cases, sometimes fatal, of gastrointestinal perforation have been reported in patients treated with ramucirumab, and ramucirumab must be permanently discontinued in such patients . Cases of posterior reversible encephalopathy syndrome (PRES), including fatal cases, have been rarely reported, presenting with seizures, headache, nausea/vomiting, hypertension, lethargy, confusion, blindness and other visual and neurological disturbances . Ramucirumab must be permanently discontinued in patients who experience PRES . Infusion-related reactions (IRR) were reported in clinical trials, with the majority of events occurring during or following a first or second ramucirumab infusion . Ramucirumab must be immediately and permanently discontinued for Grade 3 or 4 IRRs . Ramucirumab therapy should be temporarily discontinued for at least 4 weeks prior to elective surgery and if there are wound healing complications, until the wound is fully healed .

Contraindications

Cyramza is contraindicated in patients with known hypersensitivity to ramucirumab or to any of the excipients in the product .

Regulatory history

Cyramza was first approved on 23 July 2015 . Two strengths were registered on the Australian Register of Therapeutic Goods: the 100 mg/10 mL vial (ARTG 227351) and the 500 mg/50 mL vial (ARTG 227352), both listed on 23 July 2015 . In March 2018, the Pharmaceutical Benefits Scheme Advisory Committee recommended Cyramza for listing for advanced gastric or gastro-oesophageal junction adenocarcinomas with streamlined authority required restriction, subject to a substantial price reduction . In July 2022, the PBAC recommendation was revoked .