OBJECTIVES: Numerous treatment options are available for metastatic castration resistant prostate cancer (mCRPC) patients, yet optimal sequencing remains an unmet medical need. In the absence of head-to-head trials, Bayesian network meta-analysis (BNMA) was used to compare survival outcomes for [¹⁷⁷Lu]Lu‑PSMA‑617 (¹⁷⁷Lu-PSMA-617) vs. androgen receptor pathway inhibitors (ARPI), mitoxantrone (MIT), and cabazitaxel+prednisone (CABA) in the post-taxane mCRPC setting.

METHODS: A systematic literature review using MEDLINE, EMBASE, and Cochrane databases was conducted. Feasibility assessment was conducted to evaluate heterogeneity. Log cumulative hazard plots and Schoenfeld residual plots for each RCT were tested for proportionality of hazard (PH) for overall survival (OS) and radiographic progression-free survival (rPFS). BNMA with fixed effects model (FEM) and random effects model (REM) compared OS and rPFS for ¹⁷⁷Lu-PSMA-617 vs. comparators. Results based on FEM were preferred over REM due to limited data-points. League tables for outcomes expressed in hazard ratio (HR) with 95% credible interval (CrI) were developed to assess relative efficacy between comparators. Scenario analyses (SA) were additionally conducted to determine the robustness of the results.

RESULTS: Final analysis consisted of 6 RCTs with 4 treatment nodes, connected through a central ARPI node. For most of the studies, PH assumption was valid. BNMA (FEM) showed ¹⁷⁷Lu-PSMA-617 significantly improved OS HR vs. MIT (0.39, 95% CrI: [0.29–0.51]), ARPI (0.54, 95% CrI: [0.41–0.70]), and CABA (0.59, 95% CrI: [0.43–0.80]). ¹⁷⁷Lu-PSMA-617 showed significant benefit in rPFS HR vs. each comparator; MIT (0.30, 95% CrI: [0.21–0.43]), CABA (0.48, 95% CrI: [0.33–0.71]), and ARPI (0.53, 95% CrI: [0.37–0.75]). SA results were aligned with the primary analysis.

CONCLUSIONS: As part of the indirect treatment comparison, ¹⁷⁷Lu-PSMA-617 demonstrated a statistically significant improvement in OS and rPFS vs. comparators. Although direct comparative evidence to inform treatment selection in post-taxane mCRPC is lacking, these findings indicate that ¹⁷⁷Lu-PSMA-617 may yield improved survival outcomes for patients in this setting.