Clinical Variables Associated with PSA Response to Lutetium-177-PSMA ([177Lu]-PSMA-617) Radionuclide Treatment in Men with Metastatic Castration-Resistant Prostate Cancer.

Moran Gadot,Eshetu G Atenafu,Liran Domachevsky,Akram Saad,Tima Davidson,Meital Levartovsky,Raanan Berger,Margalit Aharon,Avraham Malki,Raya Leibowitz

doi:10.3390/cancers12051078

Abstract

Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan–Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or χ2/Fisher’s exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of <0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline ≥20% and ≥50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline >20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the ‘real-life’ setting of heavily pretreated men with mCRPC.

Highlights

Metastatic castration resistant prostate cancer, the last phase of the prostate cancer continuum, continues to be a fatal disease [1]
Prostate-specific membrane antigen (PSMA), a transmembrane protein highly overexpressed in cells of prostatic origin, is the target of several such radiopharmaceuticals, which differ in their biophysical properties
([177Lu]-PSMA-617) was found to be most promising and has emerged as the leading compound to date. [177Lu]-PSMA-617 binds with high affinity to PSMA and is a mixed beta-gamma emitter that causes cellular damage to PSMA-expressing prostate cancers cells in a relatively specific manner, sparing adjacent normal organs and tissues [4]

Summary

Introduction

Metastatic castration resistant prostate cancer (mCRPC), the last phase of the prostate cancer continuum, continues to be a fatal disease [1]. In the second half of the 2010s, there were no positive phase III randomized controlled trials, and progress seemed to have reached somewhat of a halt. Against this background, the last decade has seen the invention and development of radiopharmaceuticals that target specific membrane-bound proteins in a few types of cancer, a therapeutic approach designated ‘theranostics’. Lutetium-177-PSMA ([177Lu]-PSMA-617) was found to be most promising and has emerged as the leading compound to date (reviewed briefly in [3]). Lutetium-177-PSMA ([177Lu]-PSMA-617) was found to be most promising and has emerged as the leading compound to date (reviewed briefly in [3]). [177Lu]-PSMA-617 binds with high affinity to PSMA and is a mixed beta-gamma emitter that causes cellular damage to PSMA-expressing prostate cancers cells in a relatively specific manner, sparing adjacent normal organs and tissues [4]

Objectives

Results

Conclusion