Radium-223-dichlorid (2) – Xofigo®

• Clinical trials
  • The ALSYMPCA trial was a double-blind, randomised, controlled Phase III trial in which radium-223 dichloride + best standard care (BSC) was compared with placebo + BSC.

a) Adult patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases without known visceral metastases, in whom the disease has progressed following at least two prior lines of systemic therapy for the treatment of mCRPC (excluding LHRH analogues)

• For adult patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases without known visceral metastases, in whom the disease has progressed following at least two prior lines of systemic therapy for the treatment of mCRPC (excluding LHRH analogues), an additional benefit is not proven.
• The additional benefit of radium-223 dichloride as monotherapy or in combination with an LHRH analogue (LHRH: luteinising hormone-releasing hormone) for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases without known visceral metastases, in whom the disease has progressed following at least two prior lines of systemic therapy for the treatment of mCRPC (excluding LHRH analogues), is not proven.
• To establish the additional benefit, the pharmaceutical manufacturer submitted a retrospective comparative data analysis from the Flatiron Health database.
• Data on overall survival during treatment with radium-223 dichloride were compared with those for the active ingredients abiraterone, cabazitaxel, docetaxel and enzalutamide.
• Furthermore, the pharmaceutical manufacturer presented data on additional endpoints from the single-arm PARABO and REASSURE trials, as well as the ALSYMPCA registration trial.
• In the direct comparative registration trial ALSYMPCA, treatment with radium-223 dichloride is compared with best supportive care.
• Consequently, the appropriate comparator therapy has not been used.
• Furthermore, the patient population included in the study does not correspond to the patient population covered by the therapeutic indication, namely those who have received at least two prior treatments.
• The data from the single-arm PARABO and REASSURE trials, as well as the retrospective data analysis of the Flatiron Health database, are also not suitable for deriving any additional benefit.
• The pharmaceutical manufacturer therefore does not present any results in the dossier from directly comparative studies against the appropriate comparator therapy or from studies suitable for an adjusted indirect comparison.
• It is not possible to assess the additional benefit on the basis of the data submitted.

b) Adult patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases without known visceral metastases, for whom no other available systemic mCRPC therapy is suitable

• For adult patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases without known visceral metastases, for whom no other available systemic mCRPC therapy is suitable, additional benefit is not proven.
• The additional benefit of radium-223 dichloride as monotherapy or in combination with an LHRH analogue (LHRH: luteinising hormone-releasing hormone) for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases without known visceral metastases, for whom no other available systemic mCRPC therapy is suitable, is therefore not proven.
• To demonstrate the additional benefit, the pharmaceutical manufacturer presented the results of the ALSYMPCA study, which had already formed the basis of the resolution in the first benefit assessment procedure for radium-223 dichloride (resolution of 19 June 2014).
• The marketing authorisation for new INN (abiraterone, cabazitaxel, enzalutamide) has fundamentally changed the therapeutic landscape.
• Consequently, patients in the ALSYMPCA study would now have access to further treatment options as first-line therapy.
• Consequently, the results of the ALSYMPCA study are not transferable to the current treatment landscape.
• The pharmaceutical manufacturer therefore does not provide any data in the dossier that would enable an assessment of the additional benefit.
• The pharmaceutical manufacturer has been commissioned by the EMA to conduct a randomised, double-blind, multicentre Phase IV trial for the authorised indication.
• According to information provided by the pharmaceutical manufacturer, this study is currently still at the planning stage or under discussion with the EMA.

Courtesy translation only, please refer to the German original.