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Updated: Jan 9, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Efficacy and safety of treatments for metastatic castration-sensitive prostate cancer: A comprehensive network
Neal Shore1, Alicia K Morgans2, Noman Paracha3
1Carolina Urologic Research Center, AUC Urology Specialists, Myrtle Beach, SC, USA. nshore@auclinics.com.
Background:
Despite the proven efficacy of androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPIs) in metastatic castration-sensitive prostate cancer (mCSPC), many patients still receive ADT monotherapy due to safety concerns. This reliance on ADT monotherapy underscores the need for education on the comparative effectiveness and safety of available therapies versus ADT. We evaluated the efficacy and safety of alternative treatment combinations, incorporating final data from the recent ARANOTE Phase III trial.
Methods:
We conducted network meta-analysis (NMA) to evaluate progression-free survival (PFS) and overall survival (OS), incorporating heterogeneity assessment through subgroup analyses. Additionally, we performed a separate class effect NMA. We analysed grade 3-5 adverse events (AEs), serious AEs, and discontinuation due to AEs. We estimated hazard ratios (HRs) for efficacy, rate ratios (RRs) for safety, 95% credible intervals (CrI), and the surface under the cumulative ranking area (SUCRA) to rank treatments by efficacy and safety.
Results:
Darolutamide (DAR) + docetaxel (DOC) + ADT showed the highest effect size [HR of 0.27 (95% CrI: 0.18, 0.39)] and the highest ranking (SUCRA: 0.97) across the base case and several subgroups on the PFS outcome. On OS, DAR + DOC + ADT similarly achieved the lowest HR of 0.52 (0.43, 0.64) and the highest ranking (SUCRA of 0.95). Safety analyses showed that grade 3-5 AEs were more frequent with docetaxel combinations, with ABI + DOC + ADT having the highest risk of grade 3-5 AEs. DAR + ADT was ranked best on all safety outcomes, outperforming other doublets and comparable to ADT monotherapy.
Conclusions:
This NMA supports the superior efficacy of ARPI combinations against ADT monotherapy, for both OS and PFS. While DAR + ADT demonstrated comparable efficacy to other doublet combinations, it offered a superior safety profile, making it an effective and safe option for managing patients with mCSPC.
Insights
Androgen receptor pathway inhibitors (ARPIs) combined with androgen deprivation therapy (ADT) significantly improve outcomes in metastatic castration-sensitive prostate cancer (mCSPC). Darolutamide plus ADT offers superior safety compared to other combinations, making it a highly effective treatment option.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPIs) is effective for metastatic castration-sensitive prostate cancer (mCSPC).
- Many patients still receive ADT monotherapy due to safety concerns, highlighting a need for comparative data.
- This study evaluates alternative treatment combinations using final data from the ARANOTE Phase III trial.
Purpose of the Study:
- To compare the efficacy and safety of various treatment combinations for mCSPC.
- To educate on comparative effectiveness and safety of ARPI combinations versus ADT monotherapy.
- To incorporate final data from the ARANOTE Phase III trial into the analysis.
Main Methods:
- Network meta-analysis (NMA) was used to evaluate progression-free survival (PFS) and overall survival (OS).
- Heterogeneity was assessed through subgroup analyses, and a separate class effect NMA was performed.
- Grade 3-5 adverse events (AEs), serious AEs, and treatment discontinuation due to AEs were analyzed.
Main Results:
- Darolutamide (DAR) + docetaxel (DOC) + ADT showed the highest efficacy for PFS (HR: 0.27) and OS (HR: 0.52).
- Docetaxel combinations, particularly ABI + DOC + ADT, had a higher risk of grade 3-5 AEs.
- DAR + ADT demonstrated a superior safety profile, ranking best among treatments and comparable to ADT monotherapy.
Conclusions:
- ARPI combinations are more effective than ADT monotherapy for improving OS and PFS in mCSPC.
- DAR + ADT offers comparable efficacy to other doublet combinations with a superior safety profile.
- DAR + ADT is an effective and safe treatment option for managing mCSPC patients.
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