Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data - Beyond the Abstract
The U.S. expanded-access program (EAP; NCT04825652) was opened in April 2021 to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. Although the EAP eligibility criteria closely mirrored those from the VISION trial, the EAP lacks the rigor and standardization of clinical trial data, thus allowing for consideration of a broader and more diverse pool of patients resembling a real-world scenario. This study aimed to evaluate the efficacy and safety profile of [ 177Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial.
This retrospective analysis included 117 patients enrolled in the EAP at 4 institutions across the United States (UCLA [61/117, 52%], UCSF [9/117, 8%], Tulane [27/117, 23%], and Johns Hopkins [20/117, 17%]) with available toxicity and outcome data. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA response rates (42% vs. 46%; P = 0.50) and overall survival (median: 15.1 vs. 15.3 mo; P > 0.05).
Patients enrolled in the EAP were required to meet the eligibility criteria used in the VISION trial, which enabled an unbiased comparison of efficacy and toxicity. The high-grade toxicity rates observed in the EAP were similar to those reported in the VISION trial. This was an anticipated result since both cohorts were similarly pretreated with taxane-based chemotherapy and had similar levels of M1b disease on their baseline PSMA PET scans, both of which have been identified as risk factors for developing clinically significant myelosuppression in this patient population. The EAP patients were more heavily pretreated with ARSI, had worse ECOG performance status, and had higher proportions of lymph node involvement at baseline than the VISION patients. Taken together, these findings suggest that post-chemotherapy mCRPC patients who received [177Lu]Lu-PSMA-617 in the EAP were later in their disease trajectory than the VISION population. However, the efficacy of [177Lu]Lu-PSMA-617 was similar between the EAP and VISION, demonstrating the favorable toxicity profile and antitumor activity of [177Lu]LuPSMA-617 even in heavily pretreated late-stage mCRPC patients.
Strengths of this study include its multicentric design, the use of a prospective patient cohort, and the fact that inclusion criteria closely mirrored those from the VISION trial. Main limitations include retrospective data collection and the lack of direct comparison for statistical significance of all relevant data.
Written by: Vishnu Murthy, BA, Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA
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