ASCO GU 2025: Survival Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Receiving Lutetium-177-PSMA-617 (Lu) Based on Line of Therapy

(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13^th and 15^th 2025, was host to the Poster Session A: Prostate Cancer. Dr. Nicolas Sayegh presented Abstract 82: Survival outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177-PSMA-617 (Lu) based on line of therapy.

Dr. Sayegh began his presentation by highlighting that ¹⁷⁷Lutetium is a PSMA-targeted radiopharmaceutical that delivers beta radiation to PSMA-expressing cells. ¹⁷⁷Lu-PSMA-617 is approved for patients with mCRPC who have progressed on an ARPI and taxane-based chemotherapy, based on data from two clinical trials.^1,2 However, real-world data on its efficacy across different lines of therapy remain limited.

Clinical trials evaluating ¹⁷⁷Lu-PSMA-617 have been conducted in controlled settings, often excluding patients with significant comorbidities or other factors commonly encountered in routine clinical practice. The investigators aimed to assess survival outcomes in a real-world cohort of patients with mCRPC, particularly those who may not meet the stringent inclusion criteria of randomized trials and have progressed after multiple lines of systemic therapy.

This was a retrospective study that utilized the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. The Flatiron Health database is a longitudinal database, comprising de-identified patient-level structured and unstructured data, curated via technology-enabled abstraction.

During the study period, de-identified data were collected from approximately 280 cancer clinics (~800 sites of care). Patients were eligible if they had a diagnosis of mCRPC, received ¹⁷⁷Lu-PSMA-617 for the first time, and had at least two months of follow-up data. Additionally, patients were required to have received at least one prior line of therapy for mCRPC before initiating ¹⁷⁷Lu-PSMA-617.

Patients were excluded from this analysis if they received Lu-177 in combination with other therapies (except standard of care as permitted in VISION),¹ had incomplete data, were treated as part of a clinical trial, or were receiving treatment for other types of cancer.

The investigators calculated survival from the date patients received their first treatment with ¹⁷⁷Lu-PSMA-617. Time to next treatment (TTNT) and overall survival (OS) were summarized using Kaplan-Meier survival estimates.

Of the overall cohort of 24,105 patients with metastatic prostate cancer in the Flatiron Health electronic health record dataset, 303 diagnosed between January 2013 and November 2023 received treatment with ¹⁷⁷Lu-PSMA-617. The median age of these patients was 75 years (IQR 69–80). The majority were White non-Hispanic (69%), and most were treated in a community practice setting (82%). Most patients were covered by a commercial health plan (86%) and received ¹⁷⁷Lu-PSMA-617 in the third-line setting or later (91.4%). Baseline patient characteristics are illustrated in the table below:

For patients treated with ¹⁷⁷Lu-PSMA-617, the median time to next treatment (TTNT) was 8.5 months (95% CI, 7.3–9.8), as illustrated in the figure below. TTNT remained relatively consistent across all lines of therapy, ranging from 7.0 to 10.0 months. Notably, patients treated in the seventh-line setting (n=17) had the longest TTNT at 10 months, while those who received ¹⁷⁷Lu-PSMA-617 in the second-line setting (n=26) had a TTNT of 8.5 months.

The median OS was 12 months (95% CI, 11–15). Patients treated with ¹⁷⁷Lu-PSMA-617 in the third-line setting (n=77) had the longest median OS at 17 months, followed by those in the fifth- and sixth-line settings (n=64 and n=28), both at 13 months. In contrast, patients who received ¹⁷⁷Lu-PSMA-617 in the eighth-line setting (n=6) had the shortest OS at 3.7 months as shown below.

The table below, summarizes the median TTNT and OS by line therapy in patients with mCRPC treated with ¹⁷⁷Lu-PSMA-617 in a real world-setting.

Dr. Sayegh concluded their presentation by stating that:

¹⁷⁷Lu-PSMA-617 demonstrates clinical activity in patients with mCRPC beyond controlled clinical trial settings and regardless of the line of therapy.
• The slightly lower OS in this real-world study (median OS: 12 months vs. 15.3 months in VISION) may reflect differences in patient selection, including a more heterogeneous population with varying disease burdens and comorbidities.
• These findings may help inform patient counseling, treatment decision-making, prognosis discussions, and therapy selection in the outpatient setting.

Presented by: Nicolas Sayegh, MD, Postdoctoral Research Fellow at Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.

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