Survival outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium Lu 177 vipivotide tetraxetan (Lu) by prior taxane exposure.

101 Background: Lu is a prostate-specific membrane antigen (PSMA)-targeting radioligand therapy. Its approval was recently expanded to include all adults with PSMA-positive mCRPC who have been treated with an androgen receptor pathway inhibitor (ARPI) and are considered appropriate to delay taxane-based chemotherapy. With approval expanding to taxane-naïve pts, there is limited data to guide the sequencing of treatment in pts with PSMA-positive mCRPC after progression on ARPI. Thus, we sought to compare the survival of pts with mCRPC who received Lu based on the timing of taxane receipt. Methods: This is a retrospective cohort study using the US-based, electronic health record-derived deidentified Flatiron Health Research Database. We included pts diagnosed with mCRPC with prior ARPI treatment who initiated Lu from 12/19/2018 to 6/23/2025. The final cohort was divided into three categories based on the receipt of taxane relative to Lu: before Lu, after Lu, and never. Endpoints: median real world time to next therapy (rwTTNT) and median real world overall survival (rwOS) and were calculated from timing of Lu initiation, summarized by Kaplan-Meier estimates and their 95% confidence intervals (CIs). Results: Of the overall cohort of 27,979 pts with metastatic prostate cancer, 850 pts with mCRPC and prior treatment with an ARPI who received Lu were included in our analysis. The majority were White non-Hispanic (65.18%), treated in community practice (70.35%), and covered by commercial insurance (61.18%). 466 pts (54.82%) received taxane before Lu, 35 (4.12%) received taxane after Lu, and 349 (41.06%) received Lu and did not receive taxane. The median rwTTNT and rwOS by timing of taxane are summarized in the Table. Conclusions: Numerical differences in rwTTNT and rwOS were observed with Lu based on timing of taxane treatment. This may represent underlying patient and disease heterogeneity along with tumor evolution. Regardless of prior taxane exposure or not, Lu maintained effectiveness in pts with mCRPC. These results provide real-world data for patient counseling in clinic and emphasize the need for randomized clinical trials in this setting for optimal treatment sequencing. Median rwTTNT and median rwOS from first Lu initiation based on timing of taxane. N Median rwTTNT (months) (95% CI) Median rwOS (months) (95% CI) Taxane before Lu 466 8 (7.4-9.0) 12 (11-13) Taxane after Lu 35 6 (4.9-8.0) 16 (13-not reached) Never received taxane 349 10 (9.2-11) 14 (13-17)