To compare the efficacy of enzalutamide + androgen-deprivation therapy (ADT) versus apalutamide + ADT in metastatic hormone-sensitive prostate cancer (mHSPC) using a matching-adjusted indirect comparison (MAIC).
Individual patient data from patients with ≥1 confirmed bone metastasis in ARCHES (NCT02677896; enzalutamide + ADT vs placebo + ADT; n = 971) were adjusted to match baseline characteristics of patients in TITAN (NCT02489318; apalutamide + ADT vs placebo + ADT; N = 1052). Overall survival (OS), radiographic progression-free survival (rPFS), and time to prostate-specific antigen progression (TTPP) were assessed using Cox regression with placebo + ADT as the common comparator. Hazard ratios (HRs) were reported with apalutamide as the reference.
This MAIC suggested similar estimated efficacy between enzalutamide and apalutamide for OS (HR: 0.81, 95% confidence interval [CI]: 0.58-1.15) and TTPP (HR: 0.65, 95% CI: 0.41-1.03). Patients treated with enzalutamide + ADT had improved rPFS versus those treated with apalutamide + ADT (HR: 0.66, 95% CI: 0.45-0.98), but differences were not significant in sensitivity analyses aligning assessment methods.
This analysis suggested broadly similar efficacy between enzalutamide and apalutamide in patients with mHSPC. Findings should be interpreted in the context of inherent MAIC limitations.
What is this article about? Metastatic prostate cancer is cancer that starts in the prostate and spreads to other parts of the body. A common treatment for this cancer is androgen-deprivation therapy (ADT), which lowers testosterone levels to stop or slow the growth of the cancer. When cancer still responds to this treatment, it is known as metastatic hormone-sensitive prostate cancer (mHSPC).Enzalutamide and apalutamide are hormone-based medicines used with ADT to treat mHSPC. So far, no clinical trial has directly compared these two therapies. Because of this, we used a statistical method to indirectly compare these therapies using data from two separate clinical trials: the ARCHES trial, which compared enzalutamide plus ADT with placebo, and the TITAN trial, which compared apalutamide plus ADT with placebo. This method balanced patient characteristics so that the trials’ outcomes could be compared.What were the results of the study? We found that the length of time participants remained alive, and the length of time before prostate-specific antigen levels began to rise, were similar with enzalutamide plus ADT and apalutamide plus ADT. The length of time that cancer did not progress based on the results of imaging scans was longer in adults treated with enzalutamide plus ADT, but when additional analyses used a consistent way to measure progression, this improvement was no longer seen.What do the results of the study mean? These findings suggest that enzalutamide and apalutamide provide broadly similar treatment benefits when used with ADT in mHSPC.
Future oncology (London, England). 2026 Jul 29 [Epub ahead of print]
Arun A Azad, Bhavik J Pandya, Hemant Singh Bhadauria, Erhan Berrak, Vagia Daki, Paulo Martins, Janet Kim, Alexis Serikoff, Gianluca Baio, Andrew J Armstrong
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Medical Affairs, Astellas Pharma Global Inc., Northbrook, IL, USA., EMEA Real World Methods and Evidence Generation, IQVIA, Athens, Greece., EMEA Real World Methods and Evidence Generation, IQVIA, Lisbon, Portugal., Department of Statistical Science, University College London, London, UK., Center for Prostate & Urologic Cancers, Duke Cancer Institute, Durham, NC, USA.