Matching-adjusted indirect treatment comparison of the efficacy of enzalutamide versus apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer.

To date, the efficacy of the androgen receptor inhibitors enzalutamide and apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) has not been compared directly in a clinical trial setting. Indirect comparisons can be used to assess relative efficacy and provide important information to guide treatment decisions. PROSPER and SPARTAN were double-blind, randomized, placebo-controlled, phase III trials in patients with nmCRPC with overall similar study designs and inclusion and exclusion criteria. Using an anchored matching-adjusted indirect comparison, based on the final data from the PROSPER and SPARTAN studies, we assessed the comparative efficacy of enzalutamide and apalutamide, both plus androgen deprivation therapy.

Using placebo as the common comparator, individual patient data from PROSPER were matched to the aggregate patient data from SPARTAN and efficacy endpoints from PROSPER were re-weighted accordingly. Patient baseline characteristics and endpoints were clinically and statistically tested to identify potential effect modifiers, according to National Institute for Health and Care Excellence guidelines. Hazard ratios for overall survival (OS), metastasis-free survival (MFS), and time to chemotherapy (TTCx) were re-estimated for PROSPER using weighted Cox proportional hazards models and indirectly compared with those of SPARTAN using a Bayesian network meta-analysis.

Estimated hazard ratios [95% credible interval (CrI)] for enzalutamide versus apalutamide were 0.80 (95% CrI 0.58-1.10) for OS, 0.94 (95% CrI 0.69-1.29) for MFS2, and 0.90 (95% CrI 0.63-1.29) for TTCx. Similar results were seen for sensitivity analyses conducted for OS and MFS. Bayesian probability analyses showed a 91.7% favoring enzalutamide for OS, 65.1% for MFS, and 71.4% for TTCx.

The results of this matching-adjusted indirect comparison of final data from PROSPER and SPARTAN indicate comparable efficacy of enzalutamide and apalutamide with potentially a greater probability of longer MFS, OS, and TTCx in patients with nmCRPC treated with enzalutamide versus apalutamide.

ESMO open. 2022 Jun 14 [Epub ahead of print]

B Tombal, C N Sternberg, M Hussain, A Ganguli, Y Li, R Sandin, H Bhadauria, M Oh, F Saad

Institut de Recherche Clinique (IREC), Cliniques Universitaires Saint-Luc, Brussels, Belgium. Electronic address: ., Englander Institute for Precision Medicine, Weill Cornell Medicine, Sandra and Edward Meyer Cancer Center, New York, USA., Lurie Cancer Center, Northwestern University, Chicago, USA., HEOR, Oncology, Medical Affairs, Astellas Pharma Inc., Chicago, USA., Solutions UK IQVIA, London, UK., Global Health and Value, Outcomes and Evidence, Oncology, Pfizer AB, Sollentuna, Sweden., Department of Surgery, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Canada.

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