[177Lu]Lu-PSMA-617 is a radiopharmaceutical that emits beta-minus radiation and targets prostate-specific membrane antigen (PSMA)-positive prostate cancer. Despite its clinical success, there are still patients not showing sufficient response rates. This review compiles latest studies aiming at therapy improvement in [177Lu]Lu-PSMA-617-naïve and -resistant patients by alternative or combination treatments.
A variety of agents to combine with [177Lu]Lu-PSMA-617 are currently under investigation including alpha radiation-emitting pharmaceuticals, radiosensitizers, taxane chemotherapeutics, androgen receptor pathway inhibitors, immune checkpoint inhibitors, and external beam radiation. Actinium-225 (225Ac)-labeled PSMA-targeting inhibitors are the most studied pharmaceuticals for combination therapy or as an alternative for treatment after progression under [177Lu]Lu-PSMA-617 therapy. Alpha emitters seem to have a potential of achieving a response to PSMA-targeting radionuclide therapy in both initial non-responders or responders to [177Lu]Lu-PSMA-617 later developing treatment resistance. Emerging evidence for immunostimulatory effects of radiopharmaceuticals and first prospective studies support the combination of [177Lu]Lu-PSMA-617 and immune checkpoint inhibition for late-stage prostate cancer.
Current oncology reports. 2023 Oct 20 [Epub ahead of print]
Daria Arbuznikova, Matthias Eder, Anca-Ligia Grosu, Philipp T Meyer, Christian Gratzke, Constantinos Zamboglou, Ann-Christin Eder
Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany., Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. ., Department of Radiation Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Department of Urology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.