Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis.

Fadi Khreish,Stephan Maus,Ina Hierlmeier,Tobias Stemler,Samer Ezziddin,Johannes Linxweiler,Florian Rosar,Mark Bartholomä,Jonas Krause

doi:10.3390/pharmaceutics13050722

Fadi Khreish, Stephan Maus + Show 7 more

Open Access

https://doi.org/10.3390/pharmaceutics13050722

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Journal: Pharmaceutics	Publication Date: May 14, 2021
Citations: 26	License type: CC BY 4.0

Affiliation: Saarland University

Abstract

The use of 225Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with 177Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in 177Lu-naive mCRPC patients (n = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [68Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one [225Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort.

Highlights

Patients with metastatic prostate carcinoma are initially treated with androgen deprivation therapy (ADT), but a considerable number of patients reach the stage of metastatic castrationresistant prostate carcinoma [2,3]
We report on the efficacy and safety profile of [225 Ac]Ac-prostate-specific membrane antigen (PSMA)-617 augmentation in the initial phase of [177 Lu]Lu-PSMA-617 radioligand therapy (RLT) in patients with highly advanced metastatic castration-resistant prostate carcinoma (mCRPC)
2, and the relative changes are illustrated as a waterfall tial remission and two as progressive disease plot in

Summary

Introduction

Patients with metastatic prostate carcinoma are initially treated with androgen deprivation therapy (ADT), but a considerable number of patients reach the stage of metastatic castrationresistant prostate carcinoma (mCRPC) [2,3]. Bone and lymph node metastases are the most dominant, but visceral, especially liver metastases, are quite frequent [4,5]. In the stage of mCRPC, taxane-based chemotherapy (docetaxel and cabazitaxel) [6,7], treatment with novel androgen axis drugs (NAAD) (abiraterone or enzalutamide) [8,9] and bone-seeking 223 Ra therapy (Xofigo® ) [10] are currently the standard treatment options [11], which are approved by the European Medicines Agency (EMA) and the US Food and

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