German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

Abstract

177 Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castrationresistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177 Lu-PSMA-617 in a large cohort of patients. Methods: One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with 177 Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline $ 50% from baseline to at least 2 wk after the start of RLT. Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. Conclusion: The present retrospective multicenter study of 177 Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.

Repeated 177Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

“…If toxicities were comparable to the placebo group of the ALSYMPCA-trial (14), individual dose escalations for non-responders were considered ethically justified, resulting in a short learning-phase using heterogeneous dosing regimens between respective dose escalation groups. Data of these heterogeneous interim patients were not suitable for this kind of systematical evaluation, nevertheless some have been made public available within other publications (8,15). The chronology how this dose escalation was embedded into clinical practice is summarized in Fig.…”

Glu-Ureido–Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers

“…In parallel, another theranostic PSMA radioligand, PSMA for imaging and therapy (PSMA I&T), was also described (22,23). 177 Lu-PSMA-617 and the 225 Ac-labeled version are currently the main candidates for endoradiotherapy (i.e., PSMA RLT) of PC (24)(25)(26)(27). Because of large numbers of patients and the hitherto limited capacity for the production of the radiometal-based PET tracer 68 Ga-PSMA-11, there is also a need for 18 F-labeled PSMA ligands.…”

Clinical History of the Theranostic Radionuclide Approach to Neuroendocrine Tumors and Other Types of Cancer: Historical Review Based on an Interview of Eric P. Krenning by Rachel Levine

“…The observation of frequent, persistent PSMA expression in such patients has provided the rationale for the recent introduction of PSMA radioligand therapy, with very promising initial results (46,65).…”