According to current studies, the advantages in endpoint categories such as mortality, morbidity, and health-related quality of life are not offset by disadvantages in darolutamide treatment.
Adult men with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastases, have usually continued conventional androgen deprivation therapy (ADT) and waited for metastases to develop. In an early benefit assessment, the German Institute for Quality and Efficiency in Health Care (German acronym: IQWiG) has now investigated whether the addition of the active substance darolutamide offers patients an additional benefit compared with this appropriate comparative therapy.
As the advantages in terms of overall survival, symptoms, and complications, and health-related quality of life are not offset by disadvantages, there is evidence of a considerable additional benefit.
The early benefit assessment is based on data from the still ongoing randomized ARAMIS study, in which darolutamide in combination with ADT is compared with a placebo treatment in combination with ADT. The study included adult men with high-risk nmCRPC who had either had both testicles removed or who maintained their drug-induced ADT in addition to the study medication (darolutamide or placebo).
The study was double-blind until metastasis or the onset of unacceptable toxicity. After unblinding, patients were able to continue with their darolutamide plus ADT treatment if they so wished or received darolutamide instead of the placebo. There were no restrictions with regard to other follow-up therapies.
In the benefit assessment, the first of two data sections were used for all endpoints except overall survival. For the second data section, evaluations are not available for all included endpoints. Moreover, the follow-up in the study is systematically shortened for all endpoints except overall survival. In addition, a large number of subjects (and a different number in the two study arms) had already discontinued treatment in the first data section, and after the first data section, many patients switched from the placebo-plus-ADT arm to the darolutamide plus-ADT arm.
The certainty of results is estimated to be high for overall survival and low for all other endpoints. Accordingly, there is an indication of a significant additional benefit in the endpoint category mortality. In the other endpoint categories, however, there is at most a slight indication. The additional benefit ranges from considerable to significant for morbidity (symptoms and secondary complications) and low for health-related quality of life. In the adverse drug reaction category, there is no evidence of less or greater harm from the new active substance.
Overall, therefore, there is evidence of a significant additional benefit of darolutamide plus ADT compared with an observant approach while maintaining existing conventional ADT.
IQWiG. [A20-43] Darolutamide (prostate cancer) - Benefit assessment according to §35a Social Code Book V.