Background and importance Apalutamide, enzalutamide and darolutamide have recently been approved for treating castration resistant non-metastatic prostate cancer (nmCRPC). The lack of direct comparisons makes the selection and positioning of these drugs in this new scenario difficult. Taking into account the social and economic importance, it is essential to develop studies that provide answers to this lack of information.
Aim and objectives The aim of this study was to compare the relative efficacy of darolutamide versus apalutamide and enzalutamide using clinical trial data to determine the positioning of new antiandrogenic drugs in the treatment of nmCRPC.
Material and methods We performed adjusted indirect comparisons using Bucher´s method. We selected the main clinical trial for each drug (ARAMIS, PROSPER and SPARTAN trials). The three studies had a similar design and included populations with similar characteristics. The main outcome used was metastasis free survival (MFS). MFS was demonstrated to be an adequate surrogate variable for overall survival.1 The variable used for darolutamide in the darolutamide versus enzalutamide IC was progression free survival (PFS) due to the PROSPER design. MFS and PFS were compared with placebo in the three studies.
Results The three drugs were superior to placebo for the endpoints analysed. In the comparison between enzalutamide (MFS=36.6 months (m) vs 14.7 m) versus darolutamide (PFS=36.8 m vs 14.8 m), HR calculated using Bucher’s method favoured enzalutamide (0.76 (IC 0.59–0.98); p=0.037). In the IC darolutamide (MFS=40.4 m vs 18.4 m) versus apalutamide (MFS= 40.5 m vs 14.7 m) HR favoured apalutamide (1.41 (IC 1.07–1.87); p=0.015). Both IC yielded a statistically significant result.
Conclusion and relevance While indirect comparisons had limitations, this analysis showed the slight superiority in HR in delaying the appearance of metastases for enzalutamide and apalutamide. Despite the data obtained, the inferiority of darolutamide cannot be assured. The biases involved in the comparison may have influenced the results. Real world data are needed to expand our knowledge of castration resistant non-metastatic prostate cancer treatment.
References and/or acknowledgements
Xie W, Regan MM, Buyse M, et al. Metastasis-free survival is a strong surrogate of overall survival in localised prostate cancer. J Clin Oncol 2017;35:3097–104.
Conflict of interest No conflict of interest
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