Indirect treatment comparisons of darolutamide plus docetaxel and androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer

Androgen deprivation therapy (ADT) has long been the standard-of-care for metastatic, hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel (DOC) and/or androgen receptor axis–targeted therapies (ARATs) such as darolutamide (DAR), enzalutamide (ENZ), apalutamide (APA), abirateone (ABI), and rezvilutamide (REZ) has been shown to significantly improve overall survival (OS) over standard-of-care in mHSPC, including standard of care plus DOC. We indirectly compared OS and progression-free survival (PFS) of DAR+DOC+ADT against approved comparators in China using Bayesian network meta-analysis. Comparator treatment data derived from published trials (identified via Medline, EMBASE, and Cochrane Library searches) and included ENZ, APA, DOC, ABI, and REZ, each with ADT. Sensitivity analysis assumed Standard Nonsteroidal Antiandrogen (SNA)+ADT efficacy was equivalent to ADT. Fixed and random effects analyses were performed in intention-to-treat (ITT) and high-volume populations. Results were summarized using hazard ratios (HRs) relative to DAR+DOC+ADT. HRs numerically favoured DAR+DOC+ADT on all comparisons. HRs on OS (fixed effects) strongly favoured DAR+DOC+ADT against DOC+ADT (0.68 [95% CrI: 0.57–0.80]), ADT (0.55 [0.44–0.67]), and SNA+ADT (0.44 [0.28–0.70]) in ITT population; similar results were observed in high-volume population in addition to APA+ADT (0.69 [0.50–0.96]). Excluding the comparison against ABI+ADT (ITT population; random effects), which was not statistically significant, HRs on PFS strongly favoured DAR+DOC+ADT on all comparisons. Outcome definition on PFS varied across trials and is a limitation in mHSPC comparisons. Results numerically favoured DAR+DOC+ADT on OS and PFS across all comparisons, with strong evidence against APA+ADT (in the high-volume population only), DOC+ADT, ADT, and SNA+ADT on OS and all comparators on PFS (excluding ABI+ADT in ITT). Findings support the continued use of DAR+DOC+ADT as frontline treatment in mHSPC, particularly in China where REZ is approved.