XOFIGO

What it is

XOFIGO is a solution for injection containing radium (223Ra) dichloride 6.6 MBq per 6 mL. Ra-223 is an alpha particle-emitter with a half-life of 11.4 days. XOFIGO is a therapeutic alpha particle-emitting pharmaceutical with targeted anti-tumour effect on bone metastases. The active moiety of XOFIGO is the isotope Ra-223 (as Ra-223 dichloride), which mimics calcium and selectively targets bone, specifically areas of bone metastases, by forming complexes with the bone mineral hydroxyapatite. The high linear energy transfer of alpha particles (80 keV/micrometre) leads to a high frequency of double-strand DNA breaks in adjacent cells of the tumour and the bone microenvironment such as tumour promoting osteoblasts and osteoclasts, resulting in a potent and localised anti-tumour effect.

Approved indications

— Treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease .

Dosing overview

The dose regimen of XOFIGO is 55 kBq per kg body weight, given at 4 week intervals for 6 injections. XOFIGO is to be administered by slow intravenous injection (generally up to 1 minute). No dose adjustment is considered necessary in the elderly or in patients with renal or hepatic impairment.

Key safety warnings

Bone marrow suppression, notably thrombocytopenia, neutropenia, leucopenia and pancytopenia, has been reported in patients treated with XOFIGO. Haematological evaluation of patients must be performed at baseline and prior to every dose of XOFIGO. Before the first administration of XOFIGO, the absolute neutrophil count (ANC) should be ≥ 1.5 x 10⁹/L, the platelet count ≥ 100 x 10⁹/L and haemoglobin ≥ 100 g/L. XOFIGO increases the risk of bone fractures. In a clinical study, the addition of XOFIGO to abiraterone acetate and prednisone/prednisolone increased the incidence of fractures approximately three-fold in the XOFIGO arm. Increased fracture risk has been found especially in patients with medical history of osteoporosis and in patients with less than 6 bone metastases. Preventive measures such as the use of bisphosphonates or denosumab should be considered before starting or resuming treatment with XOFIGO. In patients with untreated imminent or established spinal cord compression, treatment with standard of care, as clinically indicated, should be completed before starting or resuming treatment with XOFIGO. Safety and efficacy of XOFIGO in patients with Crohn's disease and with ulcerative colitis have not been studied.

Contraindications

XOFIGO is contraindicated in combination with abiraterone acetate plus prednisone/prednisolone. An increased incidence of fractures (28.6% vs 11.4%) and deaths (38.5% vs 35.5%) was observed in patients receiving XOFIGO in combination with abiraterone acetate plus prednisone/prednisolone compared to patients receiving placebo in combination with abiraterone acetate plus prednisone/prednisolone.

PBS listing

The PBAC recommended listing in November 2017 for treatment of metastatic castrate resistant prostate cancer on a cost-minimisation basis with abiraterone, joining the same Risk Sharing Arrangement as abiraterone and enzalutamide. However, this recommendation was rescinded by the PBAC in November 2021.

Regulatory history

XOFIGO was first listed on the ARTG on 20 May 2014. The AusPAR approval date was 13 May 2014 for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. The PBAC recommended XOFIGO in November 2017 for metastatic castrate resistant prostate cancer on a cost-minimisation basis. The PBAC's recommendation was rescinded in November 2021.