PD16-11 COMPARISON OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)-TARGETED RADIONUCLIDE THERAPY (TRT) WITH LUTETIUM-177 ( 177 LU) VIA ANTIBODY J591 VS SMALL MOLECULE LIGAND PSMA-617

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (PD16)1 Apr 2020PD16-11 COMPARISON OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)-TARGETED RADIONUCLIDE THERAPY (TRT) WITH LUTETIUM-177 (177LU) VIA ANTIBODY J591 VS SMALL MOLECULE LIGAND PSMA-617 Muhammad Junaid Niaz*, Myrto Skafida, Joseph Osborne, David Nanus, Anna Molina, Charlene Thomas, Shankar Vallabhajosula, Paul Christos, Neil Bander, and Scott Tagawa Muhammad Junaid Niaz*Muhammad Junaid Niaz* More articles by this author , Myrto SkafidaMyrto Skafida More articles by this author , Joseph OsborneJoseph Osborne More articles by this author , David NanusDavid Nanus More articles by this author , Anna MolinaAnna Molina More articles by this author , Charlene ThomasCharlene Thomas More articles by this author , Shankar VallabhajosulaShankar Vallabhajosula More articles by this author , Paul ChristosPaul Christos More articles by this author , Neil BanderNeil Bander More articles by this author , and Scott TagawaScott Tagawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000859.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PSMA is established for TRT with either monoclonal antibodies (mAb) or small molecule ligands. The molecular weight, pharmacokinetics, and biodistribution of mAb vs ligands are different: mAb has long circulating blood pool time and ligands target areas of normal PSMA expression with limited accessibility to large mAbs (e.g., salivary/lacrimal glands, small bowel, and kidney). METHODS: To compare outcomes from PSMA-TRT using J591 and PSMA-617, we analyzed individual subject data elements from prospective clinical trials in mCRPC. All-grade treatment-emergent adverse events (TEAEs) and PSA changes were extracted with updated survival. Chi-squared or Fisher’s exact test was used to assess TEAEs and treatment type; multivariable logistic regression used to assess treatment and PSA response. Kaplan-Meier overall survival (OS) analysis utilized with comparisons using log-rank test. Multivariable cox proportional hazards regression analysis used to evaluate OS controlling for variables of interest. RESULTS: 131 men treated with 177Lu-J591, 50 treated with 177Lu-PSMA-617. In TEAE analysis, heme TEAEs more common with 177Lu-J591 mAb: neutropenia in 102 (77.9%, 21% Gr 4) vs. 2 (4%), p<0.001; anemia in 101 (77.1%, 11% Gr 3) vs. 8 (16%), p< 0.001, and thrombocytopenia in 118 (90.1%, 37% Gr 4) vs. 10 (20%), p< 0.001. Non-heme TEAE’s more common with ligand: xerostomia in 29 (58%) with PSMA-617 vs. 0 with J591, p<0.001 and nausea in 21 (42%) vs. 19 (14.5%), p<0.001. As dose-response effect is known, after controlling for dose, still more heme TEAEs with mAb targeting (p<0.001) and non-heme more common with ligand (p<0.001). In exploratory analysis, PSMA-617 ligand had more >30% PSA decline, adjusted odds ratio = 6.37 [95% CI 2.97-14.46], adjusting for dose and CALGB prognostic group. Median OS with PSMA-617 was shorter than J591 (14.2 vs. 19.63 months, respectively), but on multivariable analysis only higher dose (hazard ratio [HR] = 0.66, 95% CI 0.46-0.94) and subsequent receipt of FDA-approved life prolonging therapies (HR=0.65, 95% CI 0.46-0.94) significant for OS. CONCLUSIONS: As predicted based upon physical properties leading to different biodistribution, PSMA-TRT via mAb or small molecule ligand is associated with different toxicity profiles. While ligand may be associated with more PSA decline, there is no difference in OS and administering a higher dose of radionuclide is associated with longer OS regardless of type of PSMA-targeting used. Source of Funding: Prostate Cancer Foundation, National Institutes of Health (ULI RR024996, 1-KL2-RR024997-01, PTBF5405), Department of Defense (W81XWH-04-1-0267), H. Koch Foundation, Peter M. Sacerdote Foundation, Robert Dow Foundation, Larry and Carol Zicklin Philanthropic Fund, Endocyte, Weill Cornell Medical College. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e367-e367 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Muhammad Junaid Niaz* More articles by this author Myrto Skafida More articles by this author Joseph Osborne More articles by this author David Nanus More articles by this author Anna Molina More articles by this author Charlene Thomas More articles by this author Shankar Vallabhajosula More articles by this author Paul Christos More articles by this author Neil Bander More articles by this author Scott Tagawa More articles by this author Expand All Advertisement PDF downloadLoading ...