Purpose of the study: To report the safety evaluation of 177Lu-PSMA-617 derived from the cohort of 64 patients exposed to 177Lu-PSMA-617 in the RESIST-PC trial NCT03042312 Methods: RESIST-PC was a prospective multicenter phase 2 trial.
Patients with progressive mCRPC after ≥1 novel androgen-axis drug, either chemotherapy naïve or post-chemotherapy, with sufficient bone marrow reserve, normal kidney function, sufficient PSMA expression by PSMA PET and no visceral PSMA-negative lesions were eligible. Patients were randomized (1:1) into two activity groups (6.0 or 7.4 GBq per cycle) and received up to 4 cycles every 8 weeks. The primary safety endpoint was assessed by collecting and grading Adverse Events (AE) using the CTCAE. Patients were followed until disease progression, death, serious or intolerable AE, study termination by sponsor, patient withdrawal, lost to follow-up or 24 months after the first cycle. Results: The study was closed at enrollment of 71/200 planned patients because of sponsorship transfer. A total of 64 (90.1%) patients received at least one cycle of 177Lu-PSMA-617: 28 (36%) in Arm 1 (6.0 GBq) and 41 (64%) in Arm 2 (7.4GBq). There were 10 (43.5%), 19 (46.5%) and 29 (45.3%) patients who completed 4 cycles of 177Lu-PSMA-617 in the 6.0 GBq arm, 7.4 GBq arm, and overall, respectively. The most common treatment-emergent adverse events (TEAEs) of any grade in the 6.0 GBq arm, the 7.4 GBq arm and overall, were dry mouth (47.8%; 63.4%; 57.8%, respectively), fatigue (56.5%; 51.2%; 53.1%), nausea (52.2%; 43.9%; 46.9%), and diarrhea (13.0%; 31.7%; 25.0%). Frequencies of all other TEAEs were comparable among the 2 groups (within 10% difference). Serious possibly drug-related TEAEs were reported for 5 (7.8%) patients overall (none were considered as probably or definitely related to treatment): one subdural hematoma Grade 4, one anemia grade 3, one thrombocytopenia grade 4, one gastrointestinal hemorrhage grade 3, and one acute kidney injury grade 3. There were no clinically significant changes in vital signs in ECGs in the 2 treatment groups. No trend to creatinine increase, or increasing frequency of shifts from normal to abnormal over time for any hematologic parameter was noted. Conclusion: 177Lu-PSMA-617 was safe and well-tolerated at 6.0 and 7.4 GBq per cycle given at 8-week intervals with side effects easily managed with standard medical support. With established safety, further clinical trials applying individualized dosimetry and testing different 177Lu-PSMA-617 administration schemes (activity levels, time intervals) are needed to optimize tumor dose delivery and treatment efficacy.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2021 Jul 16 [Epub ahead of print]
Jeremie Calais, Johannes Czernin, Pan Thin, Jeannine Gartmann, Kathleen Nguyen, Wesley R Armstrong, Martin Allen-Auerbach, Andrew Quon, Shadfar Bahri, Pawan Gupta, Linda Gardner, Magnus Dahlbom, Beile He, Rouzbeh Esfandiari, David Ranganathan, Ken Hermann, Matthias Eiber, Wolfgang P Fendler, Ebrahim Delpassand
Department of Molecular & Medical Pharmacology, University of California Los Angeles., Advanced Accelerator Applications, a Novartis Company, Switzerland., Excel Diagnostics and Nuclear Oncology Center, United States., RadioMedix, Inc., United States., University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Germany., Department of Nuclear Medicine, Technical University Munich, Klinikum rechts der Isar, Germany.