Impact case study database

Prostate cancer affects 1 in 9 men in the UK, approximately 25% of whom will die from metastatic prostate cancer. Research from the ARG has meant that patients can benefit from participation in clinical trials. Those not involved in trials have benefitted from access to treatments that were not available as part of standard care. The research has also influenced clinical guidelines (locally and globally) and resulted in commercial impact through the development of Ra-223 treatment (Xofigo®).

Improving safety, efficacy, and efficiency of advanced radiotherapy in prostate cancer

The TAXIUM 1+2 trials (JOS -CI) demonstrated tolerability of Re-186 HEDP with Docetaxel, however there was no benefit on overall survival and this research strategy was discontinued, therefore averting further investment, and allowing full focus on Ra-223 a treatment for metastatic castration resistant prostate cancer.

The phase 2 (BC1-04) and phase 3 trials (ALSYMPCA) helped to determine the safety profile and efficacy of Ra-223 and were instrumental in the regulatory approval by FDA (May 2013) and EMA (September 2013). Ra-223 therapy was marketed as Xofigo®. The FDA reviewed Xofigo® under the agency’s priority review programme and is the first alpha radionuclide therapy to be approved by the FDA [S1]. Following licensing of Xofigo, it was approved by NICE for treatment in the UK [S2].

Introduction of advanced radiotherapies into clinical practice in Northern Ireland

Radiotherapies that have been introduced as a result of clinical trials include Intensity Modulated Radiotherapy (IMRT) and Image-guided radiotherapy (IGRT). The table below demonstrates the increase in delivery of advanced radiotherapies in Belfast, the primary treatment centre for cancer patients from across Northern Ireland.

Ra-223 was introduced in 2006 as part of BC1-04 trial followed by ALSYMPCA in 2008. The drug was licensed in 2014 and NICE approved in 2016. Numbers decreased as a result of new toxicity data from ERA-223 trial in 2018. At the peak, almost 300 treatments per year were administered in Belfast.

IMRT was introduced as part of the CHHiP trial in 2008. There has been steady increase in the use of this technology over the following 12 years increasing from 375 patients in 2013 to 2,389 in 2020. Now patients with multiple tumour types benefit from this therapy. [S3]

Skills gained in delivery of clinical trials have built capacity of local healthcare staff and encouraged the adoption of the cutting-edge techniques into routine practice. For example, Stereotactic Ablative Body Radiotherapy (SABR), an external beam radiotherapy which provides better tumour targeting, was introduced through the SPORT Trial as the first if its kind in the UK and led to 14 therapeutic radiographers being trained in the technique [S4].

A patient involved in the SABR trial talks about how his life has improved [S5]

He said: “If it wasn’t for this research, I simply would not be here. My family and I are so thankful to the doctors who have helped us. This treatment has allowed me to live my life again."

“I knew about the side effects of treatment, and they really frightened me, but this trial meant I had very little discomfort or complications and can return to normal life, for that I am very grateful.”

Overall, 605 men have participated in prostate cancer clinical trials in NI since 1 August 2013 allowing access to novel treatments and improving their quality of life. [S4]

Metastatic prostate cancer moves to the bones in most patients and so the development of Ra-223, which specifically targets the bone, is a breakthrough treatment. The ALSYMPCA phase 3 trial, in which O’Sullivan was Northern Ireland lead, showed that patients treated with Ra-223 had a median survival of 3.6 months more than men treated with placebo [S6] with an excellent safety profile and a 6-month delay in skeletal events (fractures or spinal compression) commonly associated with mCRPC [S6].  Belfast was the biggest recruitment centre for the trial with 44 patients recruited directly by JOS and colleagues. The NICE Radium-223 impact resource report 2016 estimated that around 360 people in England would receive Ra-223 each year [S7].

Patients have also benefitted from early access to advance radiotherapy treatments introduced as a result of trials. For example, as a result of the CHHiP trial which tested hypofractionated radiotherapy there are now new recommendations for a new standard of care for men with prostate cancer. Men now receive fewer treatments with the same results, leading to less disruption to their lives, including a reduction in hospital visits, with an average saving of 17 visits per patient. It is estimated that this will save the NHS in England at least GBP8,000,000 per year [S8]. The use of IMRT, IGRT, and hypofractionated radiotherapy are now included in NICE guidance [S9]

Policy impact

ARG research underpinned the guidance for Ra-223 therapy at the national (NICE guideline TA412) [S2,S9] and international levels including the Irish Cancer Strategy, and guidance produced by the European Association of Urology and the European Society for Medical Oncology. [S10].

Commercial Impact

Ra-223 was co-developed by Algeta ASA and Bayer Schering Pharma AG in a collaboration that started in 2009. The success of the ALSYMPCA phase 2 and phase 3 trials brought economic benefit to Algeta ASA with the positive trial results leading to acquisition of Algeta by Bayer for a sum of USD2,900,000,000 in December 2013 with Bayer claiming it was one of its top 5 most important cancer drugs at the time. [S11].

Xofigo is approved for use in more than 50 countries, including the U.S., the European Union, China and Japan [S12]. Bayer recorded sales of Xofigo of EUR270,000,000 in the 3^rd quarter of 2018. [S13]