Survival Outcomes With Lu-177 PSMA by Treatment Line and Taxane Sequencing in Prostate Cancer

Importance: Lutetium Lu 177 vipivotide tetraxetan (Lu-177) prostate-specific membrane antigen (PSMA) is a targeted radioligand therapy approved for patients with metastatic androgen pathway modulator-resistant (mAPMR) prostate cancer after progression on androgen receptor pathway inhibitors (ARPIs). Data to guide treatment sequencing are limited. Objective: To evaluate survival outcomes in patients with mAPMR prostate cancer receiving Lu-177 PSMA by line of therapy and the timing of taxane exposure. Design, Setting, and Participants: This cohort study used a deidentified electronic health record research database to obtain comprehensive longitudinal oncology data from community and academic practices across the US. Among patients with metastatic prostate cancer in the dataset, those who received Lu-177 PSMA after an ARPI between December 19, 2018, and June 23, 2025, met the inclusion criteria. The data cutoff was June 30, 2025. Exposure: Receipt of Lu-177 PSMA, stratified by line of therapy and timing of taxane exposure (before Lu-177 PSMA, after Lu-177 PSMA, or never received taxane). Main Outcomes and Measures: Primary end points were clinical time to next treatment (TTNT; defined as the time from Lu-177 PSMA initiation to next systemic therapy or death) and clinical overall survival (OS; defined as the time from Lu-177 PSMA initiation to death). Both outcomes were censored at last follow-up and estimated using the Kaplan-Meier method with 95% CIs. Results: Among the 850 patients included, the median (IQR) age was 74 (68-80) years; most were treated in community settings (598 [70.4%]) and had commercial insurance (520 [61.2%]). A total of 466 patients (54.8%) received taxane before Lu-177 PSMA, 35 (4.1%) received taxane after Lu-177 PSMA, and 349 (41.1%) never received taxane. Median clinical TTNT and clinical OS with Lu-177 PSMA were 8.0 (95% CI, 7.4-9.0) months and 12.0 (95% CI, 11.0-13.0) months for patients with taxane exposure before Lu-177 PSMA; 10.0 (95% CI, 9.2-11.0) months and 14.0 (95% CI, 13.0-17.0) months for patients who never received taxane; and 6.0 (95% CI, 4.9-8.0) months and 16.0 (95% CI, 13.0-not reached) months for patients with taxane exposure after Lu-177 PSMA, respectively. Conclusions and Relevance: In this cohort study, outcomes with Lu-177 PSMA were broadly consistent across treatment lines and taxane sequencing groups. These findings may help inform patient counseling, although prospective studies are needed to determine the optimal treatment sequencing strategy.