Real-world overall survival outcomes of lutetium (Lu ¹⁷⁷ ) vipivotide tetraxetan treatment in prostate cancer.

Abstract

5033 Background: After FDA approval on March 23, 2022, lutetium (Lu 177 ) vipivotide tetraxetan became an established treatment option for advanced prostate cancer, but real-world survival outcomes and prognostic factors remain incompletely described. Methods: We conducted a retrospective cohort study in Epic Cosmos with the largest to date reported cohort of patients with prostate cancer who initiated lutetium Lu 177 vipivotide tetraxetan after FDA approval to Dec 20, 2025, ensuring at least one month of follow-up prior to the query date. OS was measured from the medication start date to death, or censoring at last encounter. Kaplan–Meier methods were used for survival analysis. Univariable Cox proportional hazards models, adjusted for false discovery rate (FDR), were used to assess associations between OS and clinical variables. Results: The cohort included 6464 patients with a median age of 74.0 years (IQR: 38–100). The cohort was predominantly White (75.2%) and Black/African American (19.9%). Kaplan-Meier analysis showed OS probabilities of 85.4%, 67.2%, 42.8%, and 23.8% at 6, 12, 24, and 36 months, respectively, comparable to results reported in the Phase 3 VISION trial. Worse survival was significantly associated with a history of tobacco use (HR 1.22 [1.11–1.33], FDR <0.01) and higher Charlson Comorbidity Index scores (HR 1.04 [95% CI 1.02–1.06], FDR <0.01). Conversely, higher BMI (HR 0.98 [0.97–0.99], FDR <0.01) was associated with improved survival. Baseline laboratory markers of nutritional and hematologic reserve were strongly protective, including higher Albumin (HR 0.39 [0.35–0.43], FDR <0.01), Total Protein (HR 0.81 [0.74–0.89], FDR <0.01), Hemoglobin (HR 0.77 [0.75–0.79], FDR <0.01), RBC count (HR 0.53 [0.49–0.57], FDR <0.01), and MCHC (HR 0.88 [0.86–0.91], FDR <0.01). Inflammatory and immune markers showed distinct prognostic value: higher Eosinophils (HR 0.38 [0.25–0.58], FDR <0.01) and Lymphocytes (HR 0.69 [0.64–0.76], FDR <0.01) were associated with better outcomes, while higher Basophil-to-Lymphocyte Ratio (HR 2.10 [1.17–3.78], FDR = 0.02), RDW (HR 1.16 [1.14–1.19], FDR <0.01), and Neutrophils (HR 1.06 [1.04–1.08], FDR <0.01) were associated with worse survival. Higher electrolytes (Sodium, Chloride, Potassium, Bicarbonate) were generally associated with lower hazard, likely reflecting better physiologic homeostasis. Conclusions: In this large real-world cohort of prostate cancer patients treated with Lu 177 vipivotide tetraxetan, overall survival was strongly influenced by tobacco use, comorbidity burden, and baseline laboratory markers reflecting nutritional status, hematological reserves, and immunity. These findings highlight the importance of physiologic reserve and inflammatory state in shaping outcomes with this radioligand therapy and may inform risk stratification and care strategies in routine clinical practice.