ASCO 2019: RESIST-PC Phase 2 Trial: 177Lu-PSMA-617 Radionuclide Therapy for Metastatic Castrate-Resistant Prostate Cancer - Medical Oncologist Perspective

Chicago, IL ( Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in all forms of prostatic tissue with increased PSMA expression in advanced, castration-resistant tumors.1,2 The novel ligand PSMA-617 bound with lutetium 177 specifically targets PSMA positive tumor tissue. A number of ongoing trials are now examining the effectiveness of compound for patients with metastatic castration-resistant prostate cancer (mCRPC). In this investigator-initiated open-label prospective bi-centric single-arm phase 2 clinical trial, investigators describe their experience of 177Lu-PSMA-617 radionuclide therapy in patients with progressive mCRPC.

This abstract provides data on 64 patients who have mCRPC and have progressed on at least one prior line of novel androgen axis therapy (i.e. enzalutamide, abiraterone). Chemotherapy-treated and chemotherapy naïve patients were all included. Concurrent therapy was permitted and 83% of patients continued ADT, 23% of patients continued novel androgen axis therapy, and 6% of patients had concurrent immunotherapy. Patients were randomly assigned to two treatment groups – 6.0 or 7.4 GBq.

38% of patients had a PSA50 at with a median time to best response of 22 weeks. The common grade 3 toxicities were nausea and vomiting (6%), anemia (8%), leukopenia (5%), kidney failure (3%), thrombocytopenia (3%), and neutropenia (3%). 45% of patients completed all 4 cycles of 177Lu-PSMA-617. There was no significant difference in efficacy or toxicity between the two treatment doses.

177Lu-PSMA-617 is an active therapy for patients with mCRPC with acceptable toxicities. This study population was quite heterogeneous with many patients being treated concurrently with various therapies and it is thus difficult to tease out the effect of 177Lu-PSMA-617 by itself. It is unknown if a combination approach is safe or more effective and the limited sample size here limits any conclusions regarding a combination approach. ERA 223 showed that combination of abiraterone and radium led to increased bone fractures compared to abiraterone alone which suggests that combination approaches with radiotherapeutics must be studied in a controlled setting (with bone health agents when indicated) to determine safety and efficacy.

Presented by: Jeremie Calais, MD, MSc Assistant Professor at the Ahmanson Translational Imaging Division of the Department of Molecular and Medical Pharmacology UCLA Nuclear Medicine Department Los Angeles, CA

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA

  1. Chang SS. Overview of prostate-specific membrane antigen. Reviews in Urology 2004;6:S13.
  2. Tagawa ST, Vallabhajosula S, Christos PJ, et al. Phase 1/2 study of fractionated dose lutetium‐177–labeled anti–prostate‐specific membrane antigen monoclonal antibody J591 (177Lu‐J591) for metastatic castration‐resistant prostate cancer. Cancer 2019.
  3. Smith M, Parker C, Saad F, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology 2019;20:408-19.

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