Aim: Recent network meta-analyses (NMAs) in metastatic castration-sensitive prostate cancer have not adequately addressed potential treatment effect modifiers and population imbalances, which introduces bias. Although, individual-patient data (IPD) are seldom available across all trials, recent methodological advances allow adjustments using a combination of IPD and aggregate data. Materials & methods: IPD from the ARASENS trial (darolutamide + docetaxel + androgen-deprivation-therapy [ADT]) and aggregate data from a systematic review were analyzed. Two methods were used to adjust for population imbalances: multilevel network meta-regression (ML-NMR) using baseline characteristics, and network meta-interpolation (NMI) using subgroup data. Relative effects were estimated for an ARASENS-like population, with sensitivity analysis in an average trial population. Results: Twelve studies, including ARASENS, were included. All studies reported baseline characteristics for ML-NMR. Sufficient subgroup data for NMI were available in 8/12 studies for overall survival (OS) and 5/12 studies for progression-free survival (PFS). Darolutamide + docetaxel + ADT showed significant benefit over docetaxel + ADT, ADT and standard-nonsteroidal-antiandrogen + ADT in all analyses. ML-NMR showed improved OS for darolutamide + docetaxel + ADT compared with abiraterone + docetaxel + ADT, apalutamide + ADT, enzalutamide + ADT and abiraterone + ADT. ML-NMR also showed improved PFS for darolutamide + docetaxel + ADT compared with apalutamide + ADT and enzalutamide + ADT. Using NMI, darolutamide + docetaxel + ADT demonstrated OS benefit over abiraterone + ADT and PFS benefit relative to abiraterone + ADT and apalutamide + ADT. Findings were consistent in an average population, although ML-NMR did not show significant OS benefit of darolutamide + docetaxel + ADT over apalutamide + ADT. Conclusion: Improved outcomes were observed with darolutamide + docetaxel + ADT compared with other therapies. By incorporating effect modifiers and addressing population imbalances, we provide clinicians with a more accurate understanding of treatment efficacy for better-informed decision-making.
What is this article about? This study examines different statistical methods for comparing treatments for metastatic castration-sensitive prostate cancer across multiple trials, taking into account differences among patients, such as age and health status. We evaluated different statistical approaches to adjust for these varying patient characteristics and assessed their strengths and limitations in producing reliable treatment comparisons. The study presents results for key clinical outcomes, including overall survival and progression-free survival. What were the results? Our findings provide evidence that the combination of darolutamide, docetaxel and androgen-deprivation-therapy (ADT) improves survival rates for patients with metastatic castration-sensitive prostate cancer compared with other treatment options. What do the results mean? The findings suggest that patients receiving the darolutamide, docetaxel and ADT combination therapy may live longer and have better outcomes, aiding doctors in making informed treatment choices.
Journal of comparative effectiveness research. 2026 Jan 06 [Epub]
Neal Shore, Alicia K Morgans, Noman Paracha, Howard Thom, Edna Keeney, Philip Orishaba, David Phillippo, David Aceituno, Christopher Jd Wallis, Elaine Gallagher, Martin Boegemann
Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA., Dana-Farber Cancer Institute, Boston, MA, USA., Bayer Pharmaceuticals, Basel, Switzerland., Clifton Insight, Bristol, UK., University of Bristol, Bristol, UK., Division of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada., University of Muenster Medical Center, Department of Urology, Muenster, Germany.