Real life experience of compassionate use of 177Lu-PSMA-1 for metastatic castration-resistant prostate cancer patients in Leon Berard Cancer Centre

Abstract

PurposeWe present a retrospective feedback of PSMA-targeted radioligands therapy (PRLT) using onsite radiolabeled 177Lu-PSMA-1 to treat metastatic castration-resistant prostate cancer patients (mCRPC) progressing after conventional treatments. MethodsOnsite radiolabeling of the PSMA-1 with 177Lu was authorized by the National Agency for the Safety of Medicines and Health Products (ANSM) after IMPD (Investigational Medicinal Product Dossier) approval allowing to treat patients before 177Lu-PSMA-617 national agreement. Patients were screened on 68Ga-PSMA and 18F-FDG PET-CTs and would be included in case of significant PSMA uptake in the majority of known lesions without mismatch between FDG and PSMA especially in liver metastases, following the THERAP trial procedure. Treatments would consist in 6 injections of 7.4GBq of 177Lu-PSMA-1 every 6 weeks following the VISION phase III trial. A clinical, biological and radiological follow-up during the treatment allowed the detection of possible adverse effects or tumor progression that should lead to treatment discontinuation, and the monitoring and characterization of the expected benefits, according to PCWG3 criteria. Whole-body SPECT-CT was performed in all patients 24hours after injection at each cycle using the VERITON® - Spectrum Dynamics to monitor lesions 177Lu-PSMA-1 uptake. ResultsBetween April 2021 and July 2022, 21 of the 24 patients screened could be included after clinical, biological and imaging screening. Ten received at least 4 injections, and 6 received all 6 injections. Three patients demonstrated a 50% reduction in PSA (PSA50), and 3 others any significant PSA evolution. The safety profile was favorable, with however grade 3 toxicities leading to permanent discontinuation of the treatment. ConclusionOn-site radiolabeled 177Lu-PSMA-1 appeared safe and lead to clinical benefit in most patients. The benefit-risk balance seems to be favorable for these multitreated mCRPC progressive patients in the absence of therapeutic alternatives. It requires a close multidisciplinary and multiprofessional collaboration within the nuclear medicine department. Further studies are necessary to specify the modalities of scans analysis, the impact of post-therapy scans, the length of the benefits observed, and the position of PRLT in the management of prostate cancers.