Progression-free survival with darolutamide and docetaxel vs. androgen receptor pathway inhibitors vs. docetaxel in metastatic hormone-sensitive prostate cancer: a real-world multicenter retrospective study
Background and objective - In metastatic hormone-sensitive prostate cancer (mHSPC), first-line treatment with either docetaxel + androgen deprivation therapy (ADT) or androgen receptor pathway inhibitors (ARPI) + ADT represented the standard of care. Triplet therapy (docetaxel + ARPI + ADT) has show...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 2026
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| In: |
Urologic oncology
Year: 2026, Volume: 44, Issue: 4, Pages: 1-11 |
| ISSN: | 1873-2496 |
| DOI: | 10.1016/j.urolonc.2026.111028 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.urolonc.2026.111028 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1078143926000396 
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| Author Notes: | Emily Rinderknecht, M.D., Gloria Bielsteina, Richard Cathomas, M.D., Katrin Schlack, M.D., Julius L.D. Bastian, M.D., Christopher Darr, M.D., Daniel Unland-Gies, M.D., Paula Kappler, M.D., Pia Paffenholz, M.D., Julika Richter, M.D., Marten Müller, M.D., Anna Katharina Seitz, M.D., Julie Steinestel, M.D., Isabel Heidegger, M.D., Ph.D., Maximilian Burger, M.D., Johannes Breyer, M.D., Marco J. Schnabel, M.D. |
| Summary: | Background and objective - In metastatic hormone-sensitive prostate cancer (mHSPC), first-line treatment with either docetaxel + androgen deprivation therapy (ADT) or androgen receptor pathway inhibitors (ARPI) + ADT represented the standard of care. Triplet therapy (docetaxel + ARPI + ADT) has shown superiority over docetaxel + ADT, leading to regulatory approval. However, real-world data directly comparing ARPI + ADT and triplet therapy are lacking. This study evaluates real-world outcomes across 3 treatment regimens using inverse probability of treatment weighting (IPTW). - Methods - We retrospectively analyzed data from 13 centers of men with mHSPC treated with docetaxel + ADT, ARPI (apalutamide or enzalutamide) + ADT, or darolutamide + docetaxel + ADT. The primary endpoint was progression-free survival (PFS); secondary endpoints included adverse events. To address baseline imbalances, IPTW was employed. Time-to-event data were analyzed using weighted Cox proportional hazards regression with robust variance estimation. - Results - After excluding incomplete cases, 346 men were analyzed: 58 (16.8%) received docetaxel + ADT, 203 (58.7%) ARPI + ADT, and 85 (24.6%) triplet therapy. Before weighting, triplet patients demonstrated more adverse baseline features. After achieving covariate balance through IPTW adjustment, no significant differences in PFS were observed, with hazard ratios of 1.60 (95% CI: 0.78-3.28, P = 0.20) for docetaxel + ADT and 0.70 (95% CI: 0.36-1.35, P = 0.29) for ARPI + ADT compared to triplet therapy. Grade ≥3 adverse events occurred in 36.2%, 10.9%, and 31.8% of patients, respectively (P < 0.001). - Conclusions - In this IPTW-adjusted real world cohort, triplet therapy was not significantly associated with improved PFS compared to ARPI + ADT or docetaxel + ADT. These findings should be interpreted in the context of limited sample size and follow-up, and further prospective studies are warranted. |
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| Item Description: | Online verfügbar 20 February 2026, Version des Artikels 20 February 2026 Gesehen am 15.05.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1873-2496 |
| DOI: | 10.1016/j.urolonc.2026.111028 |