Radium-223 dichloride: a new paradigm in the treatment of prostate cancer

Abstract

Radionuclides have been widely used for cancer treatment. Recently, new research about radium-223 dichloride has been conducted in prostate cancer, which reveals that it is the first radiopharmaceutical to demonstrate an improvement in overall survival and time to first symptomatic skeletal event in patients with castration resistant prostate cancer with symptomatic bone metastases. This fact has created a new paradigm in the treatment of prostate cancer landscape, where only chemotherapy and hormone therapy had a role, while β-emitters had been confined exclusively to the role of pain relief with no impact on survival. The aim of this review is to outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 dichloride, reviewing patients’ profile that make them suitable to therapy and chances for further studies.

Keywords:

• alpha-emitters
• bone metastases
• prostate cancer
• radiopharmaceuticals
• radium-223

Financial & competing interests disclosure

Funding for this study was provided by Bayer HealthCare. Sonia Maciá (Pivotal S.L) provided advice to properly handle and submit the paper. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Radium is a calcium mimetic bone seeker α-particles emitter able to focus on areas of increased bone turnover.

• Investigations on radium-223 (Ra-223) were conducted since Phase I revealed that its activity was related with the reduction of bone alkaline phosphatase.

• Three Phase II trials have matched primary and secondary endpoints showing a benefit in bone alkaline phosphatase, pain index, safety, serum markers of bone turnover, PSA and overall survival.

• The Phase III ALSYMPCA randomized 922 patients 2:1 to receive Ra-223 injections at 50 kBq/kg plus best standard of care versus placebo plus best standard of care. The trial was stopped based on the recommendation of an independent data monitoring committee, due to early evidence of benefit in terms of overall survival. Ra-223 significantly improved overall survival in patients with castration-resistant prostate cancer and bone metastases compared with placebo. No differences in severe side effects (grade 3–4) were observed between Ra-223 and placebo groups.

• Results are generalizable, since the ‘standard of care’ was a very wide option, including also radiotherapy.

• New biochemical markers and new imaging methods could be recommended according to the ALSYMPCA study.

• There is a strong rationale for the combination of Ra-223 with the main antitumor drugs already approved for the treatment of castration-resistant prostate cancer patients, such as docetaxel, cabazitaxel, abiraterone acetate and enzalutamide.