Treatment patterns and survival outcomes among lutetium 177–experienced patients with metastatic castration-resistant prostate cancer.

Abstract

69 Background: Survival expectations for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving late-line therapies have historically been defined by trials conducted prior to the approval of lutetium-177 vipivotide tetraxetan (Lu177). With Lu177 now established as a standard of care following Phase 3 VISION trial, treatment (tx) sequencing and survival outcomes in the post–Lu177 setting remain poorly characterized. This real-world study evaluates outcomes of mCRPC pts who required subsequent tx after Lu177. Methods: This retrospective cohort study included pts with mCRPC who initiated subsequent tx after Lu177 from 01/01/2018 to 07/31/2024 in the U.S. based EHR-derived de-identified Flatiron Health Research Database. The data cut-off date was 07/31/2025. Overall survival was measured from initiation of post-Lu177 tx (index date) until death and was calculated by the Kaplan-Meier method. Predictors of survival were identified by multivariate Cox models. Subgroups were defined by prior exposure to taxane chemotherapy. Pre/post taxane subgroups required ≥1 androgen receptor pathway inhibitor (ARPI) before index date. Post-taxane was defined as prior receipt of docetaxel or cabazitaxel in mCRPC. Results: Among 743 pts treated with Lu177, 161 (22%) initiated subsequent therapy. Of these, 65% (n=105) were post-taxane. More than 40 distinct tx regimens were identified following Lu177. The most common regimens were cabazitaxel monotherapy (19%), cabazitaxel and carboplatin (12%), and enzalutamide monotherapy (9%). Overall, 50% of pts received a chemotherapy-based regimen. The median duration of post-177Lu tx was 2.4 months. Median overall survival (mOS) was 8.0 months overall, 13.5 months in pre-taxane subgroup, and 6.8 months in post-taxane subgroup. ECOG≥2 [Hazard Ratio (HR) (95% CI)=2.6(1.4 - 4.9)] and Lu177 duration <180 days [HR=1.7(1.1 - 2.8)] were predictors of shorter survival. Conclusions: Among the mCRPC pts receiving subsequent therapy after Lu177, tx selection was heterogeneous and primarily chemotherapy-based. The short tx duration and limited survival highlights more effective therapies after Lu177 tx are needed to improve outcomes in mCRPC. Baseline disease characteristics at initiation of post-Lu177 tx and survival. Overalln=161 Pre-Taxane n=37 Post-Taxane n=105 Median Age, years 73 70 73 Metastasis SitesBoneLymph NodeLiver 149 (93%)83 (52%)30 (19%) 35 (95%)18 (49%)4 (11%) 99 (94%)59 (56%)24 (23%) ECOG ≥2 30 (19%) 5 (14%) 23 (22%) Prior mCRPC Lines of Therapy <3 3 4 >4 32 (19%)38 (24%)35 (22%)56 (35%) 19 (51%)7 (19%)6 (16%)5 (14%) 6 (6%)25 (24%)24 (23%)51 (48%) Duration of Lu177, days <180 ≥180 80 (50%)81 (50%) 21 (57%)16 (43%) 49 (47%)56 (53%) mOS (95% CI), months 8.0 (6.8 -11.5) 13.5 (6.9- NR) 6.8 (5. 5- 9.3) Prior ARPI was not required in overall cohort. Prior ARPI was required for pre/post taxane subgroups.