About Xofigo®▼ (radium-223 dichloride) in mCRPC

Xofigo is fully funded throughout the UK

Approved by NICE

Xofigo is NICE recommended as an option for treating patients with hormone-relapsed prostate cancer with 2 or more symptomatic bone metastases and no known visceral metastases if they have experienced disease progression after at least 2 lines of prior systemic therapy (other than LHRH analogues) or are ineligible for available systemic therapy options.

SMC accepted

For the treatment of adults with CRPC, symptomatic bone metastases and no known visceral metastases

To find out more, see Guidelines

mCRPC patients with symptomatic bone metastases should be treated early with Xofigo (prior to visceral metastases)

Xofigo▼ Prescribing Information

Identifying the right patients for treatment with Xofigo

Xofigo is not recommended in patients with a low level of osteoblastic bone metastases.

How Xofigo may fit in to your treatment sequence

These are illustrative algorithms based on the revised EU indication for Xofigo. Not all potential treatment options are shown. Concurrent use of bone health agents to treat osteoporosis or for patients with bone metastases is recommended. Sequential use of abiraterone and enzalutamide (or vice versa) is not considered as an option due to likely futility of treatment. Consider clinical trials or best supportive care after all available systemic therapies have been administered.

Abbreviations: ADT: androgen deprivation therapy; AR: androgen receptor; EU: European Union; LHRH: Luteinising hormone releasing hormone; mCRPC: metastatic castration-resistant prostate cancer; mHSPC: metastatic hormone-sensitive prostate cancer; nmCRPC: non-metastatic castration-resistant prostate cancer.

Use Xofigo while there is an opportunity for action before the development of visceral metastases

Xofigo + BSC significantly extended median OS vs placebo + BSC

In the phase 3 ALSYMPCA trial, an updated analysis showed that Xofigo + BSC significantly extended median OS by 3.6 month vs placebo + BSC (14.9 months vs 11.3 months, respectively; P<0.001).

Adapted from Parker C et al. 2013. ALSYMPCA was a double-blind, randomised, placebo-controlled, phase 3 study in 921 symptomatic mCRPC patients with 2 or more bone metastases. Patients were randomised 2:1 to receive 6 injections (one every 4 weeks) of Xofigo + BSC (n=614) or placebo + BSC (307). BSC included local EBRT or treatment with bisphosphonates, corticosteroids, antiandrogens, oestrogens, estramustine, or ketoconazole. The primary endpoint was overall survival.

Abbreviations: BSC: best standard of care; EBRT: external beam radiation therapy; mCRPC: metastatic castration-resistant prostate cancer; OS: overall survival.

Xofigo + BSC significantly delays time to first symptomatic skeletal event (SSE) vs placebo + BSC

In the phase 3 ALSYMPCA trial, an updated analysis of secondary endpoints showed that Xofigo + BSC significantly delayed time to first SSE by 5.8 months vs placebo + BSC (15.6 months vs 9.8 months, respectively; P<0.001).

Adapted from Parker C et al. 2013. ALSYMPCA was a double-blind, randomised, placebo-controlled, phase 3 study in 921 symptomatic mCRPC patients with bone metastases. Patients were randomised 2:1 to receive 6 injections (one every 4 weeks) of Xofigo + BSC (n=614) or placebo + BSC (307). BSC included local EBRT or treatment with bisphosphonates, corticosteroids, antiandrogens, oestrogens, estramustine, or ketoconazole. SSEs were defined as EBRT for pain relief, spinal cord compression, tumour-related orthopaedic surgical interventions, bone fractures. The primary endpoint was overall survival.

Abbreviations: BSOC: best standard of care; EBRT: external beam radiation therapy; mCRPC: metastatic castration-resistant prostate cancer; OS: overall survival; SSE: symptomatic skeletal event.

Improved survival with Xofigo + BSC is accompanied by a slower decline in quality of life vs placebo + BSC

A post hoc analysis of the phase 3 ALSYMPCA trial showed that significantly more patients treated with Xofigo + BSC experienced a meaningful improvement in quality of life (as measured by FACT-P total score or EQ-5D utility score) vs placebo + BSC (P=0.02 and P=0.004, respectively).

In addition, significantly more patients experienced pain relief with Xofigo + BSC than placebo + BSC (30.2% [129/427] vs 20.1% [37/184], respectively; P=0.01)

Adapted from Nilsson S et al. 2016. ALSYMPCA was a double-blind, randomised, placebo-controlled, phase 3 study in 921 symptomatic mCRPC patients with bone metastases. Patients were randomised 2:1 to receive 6 injections (one every 4 weeks) of Xofigo + BSC (n=614) or placebo + BSC (307). BSC included local EBRT or treatment with bisphosphonates, corticosteroids, antiandrogens, oestrogens, estramustine, or ketoconazole. The primary endpoint was overall survival. A post hoc analysis looked at health-related quality of life using two validated instruments: the general EQ-5D and the disease-specific FACT-P. Meaningful improvement defined as increase in FACT-P total score of ≥10 from baseline or an increase in EQ-5D utility score of ≥0.1 from baseline, at Week 16 and/or Week 24.

Abbreviations: BSOC: best standard of care; EBRT: external beam radiation therapy; EQ-5D: EuroQoL 5D; FACT-P: Functional Assessment of Cancer Therapy-Prostate; mCRPC: metastatic castration-resistant prostate cancer.

Safety profile of Xofigo + BSC was comparable to placebo + BSC

ALSYMPCA was a double-blind, randomised, placebo-controlled, phase 3 study in 921 symptomatic mCRPC patients with bone metastases. The safety population included 600 patients in the Xofigo + BSC group and 301 patients in the placebo + BSC group.

• The most frequently observed adverse reactions (≥ 10%) in patients receiving Xofigo were diarrhoea, nausea, vomiting, thrombocytopenia and bone fracture
• The most serious adverse reactions were thrombocytopenia and neutropenia
• Xofigo increases the risk of bone fractures. In clinical studies, concurrent use of bisphosphonates or denosumab reduced the incidence of fractures in patients treated with Xofigo

For the full list of AEs, please refer to the SMPC links below:

• GB Summary of Product Characteristics
• NI Summary of Product Characteristics

Xofigo▼ Prescribing Information

Treatment considerations

• Chemotherapy may be used after Xofigo^*

*The haematological safety profiles for patients receiving chemotherapy after Xofigo were similar to those seen in patients receiving chemotherapy after placebo.

Patient considerations

• Low incidence of Grade 3–4 vomiting
• Can be administered without the need for steroids^†

^†Xofigo is contraindicated in combination with abiraterone acetate and prednisone/prednisolone. Concomitant use of steroids may further increase the risk of fracture.

Abbreviations: AE: adverse event; BSOC: best standard of care; mCRPC: metastatic castration-resistant prostate cancer.

Xofigo has a fixed course of treatment

Xofigo is administered as a 1-minute IV injection every 4 weeks for 6 injections.

Help your patients experience the benefits of Xofigo

Use of Xofigo is not recommended in patients with low levels of osteoblastic bone metastases.

Abbreviations: OS: overall survival; SSE: symptomatic skeletal event; QoL: quality of life