177Lu-PSMA-617 Boosts Antitumor Effects in Real-World Setting for mCRPC

The phase 3 VISION trial previously showed that ¹⁷⁷Lu-PSMA-617 enhances overall survival (OS) and image-based progression-free survival (PFS) when added to standard of care treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSi).

The trial led to the approval of ¹⁷⁷Lu-PSMA-617 by the Food and Drug Administration, and the creation of an expanded access program (EAP) to provide access to the drug for eligible patients until regulatory approval was obtained.

At the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting, Vishnu Murthy presented results of a study that sought to evaluate the efficacy and safety of ¹⁷⁷Lu-PSMA-617 in a real-world setting within the EAP, and to compare the results with those from the VISION trial.

Patients enrolled in the EAP between May 2021 and March 2022 were included in the study. Each patient was administered 7.4 GBq (200 mCi) +/- 10% of ¹⁷⁷Lu-PSMA-617 once every 6 weeks for up to 6 cycles. Treatment cycles continued until disease progression, severe toxicity, or patient withdrawal.

The study analysis included the patients’ comprehensive metabolic panel, estimated glomerular filtration rate (GFR), complete blood count, and prostate specific antigen (PSA) levels within 4 weeks of each cycle and 4-6 weeks after the last cycle.

Patients were retrospectively screened for incidences of hematologic toxicity. Outcome measures included overall survival (OS) from 4 weeks before cycle 1 to date of death or last follow-up alive, and ≥50% PSA decline rates (PSA-RR). The differences between VISION and EAP patients were assessed using a t-test of proportions.

A total of 117 patients were included in the study. The number of therapy cycles were lower in patients in the EAP group versus the VISION group (median: 4 vs 5). Patients in the EAP group had a higher number of previous ARSi (>2 ARSi: 16% vs 7%; P=.002) and a higher prevalence of nodal disease on baseline PSMA PET (60% vs 50%; P=.038), and had a higher baseline PSA (median baseline PSA: 97.3 vs 77.5 ng/mL) and a higher number of previous taxane-based chemotherapy regimens (>1 taxane: 47% vs 40%; P=.16).

The EAP group had higher levels of all grade hematologic adverse events compared with the VISION group, including anemia (41% vs 32%; P=.06), thrombocytopenia (48% vs 17%; P<.001), lymphopenia (63% vs 14%; P<.001), neutropenia (31% vs 9%; P<.001), and leukopenia (46% vs 12%; P<.001). Patients in the EAP group also experienced shorter OS (median OS: 13.7 vs 15.3 months) and lower PSA-RR (40% vs 46%; P=.29).

The use of ¹⁷⁷Lu-PSMA-617 in heavily pretreated patients with late-stage mCRPC provided beneficial antitumor effect and acceptable toxicity levels in a real-world setting within an EAP.