Abstract CT015: Safety and long-term efficacy of radioligand therapy using Lu-177 labeled PSMA ligands in metastatic prostate cancer: A single center experience over 5 years
Authors: Kulkarni Harshad R. , Langbein Thomas , Atay C , Singh Aviral , Schuchardt Christiane , Lehmann Coline , Pomper Martin , Pienta Kenneth J. , Baum Richard P. 
Published: August 2018

Abstract
Aim: Metastatic prostate cancer (mPC) has still a poor prognosis. First- and second-line chemotherapy with docetaxel or cabazitaxel is often toxic and prolongs life by only a few months. Also novel agents like abiraterone, enzalutamide or Ra-223-chloride confer a limited survival benefit. Prostate-specific membrane antigen (PSMA) is a glutamate carboxypeptidase II overexpressed especially in poorly differentiated prostate cancer (1) and is a very attractive target for diagnosis and therapy (theranostics) with radiolabeled small molecules. Internalization and retention within the tumor cell provides very promising and highly selective treatment effects of multiple metastases with PSMA radioligand therapy (PRLT) (2-5).
Methods: 224 mPC patients (mean age 71 years, mean Gleason score 8), screened by Ga-68 PSMA or F-18 DCFPyl PET/CT imaging, were treated with 1 - 9 cycles (3.5 - 12 GBq Lu-177 PSMA per cycle) between April 2013 and October 2017 and included in the intention to treat analysis with a median follow-up time of 16 months (3 - 55). Previous treatments were surgery (154), external beam radiation (151), chemotherapy (110), androgen deprivation (206) and Ra-223 chloride (19). The serum prostate antigen (PSA) levels were monitored before and after therapy. Response to therapy was also determined by RECIST as well as according to molecular imaging criteria using standardized uptake values (SUV) on Ga-68 PSMA PET/CT studies. Hematological and organ toxicity was documented according to CTCAE v4.03.
Results: Reduction in serum PSA was observed in 157/224 (70%) patients; 121/224 patients (54%) demonstrated a PSA decline by &gt;50%, best response was complete remission with undetectable PSA. Ga-68 PSMA PET/CT after at least 2 PRLT cycles in 200 patients demonstrated complete remission in 6 (3%), partial remission in 70 (35%), stable disease in 55 (27.5%) and progressive disease in 69 (34.5%) patients. RECIST revealed 46 (23%) partial remissions, 6 (3%) complete remissions, 84 (42%) with stable disease and 64 (32%) disease progressions. The median overall survival was 27 months. Median progression-free survival was 18 months. No severe (G3-4) bone marrow toxicity was observed and patients didn't show any evidence of nephrotoxicity or any other significant organ toxicity. Mild xerostomia occurred in less than 3% of all patients.
Conclusion: Lu-177 PSMA radioligand therapy appears to be effective for the treatment of metastatic prostate cancer with only minimal toxicity, offering a significant benefit in overall and progression-free survival even in patients whose disease had progressed despite all standard treatments. Randomized controlled studies are required to best determine the place of this theranostic approach in the management of mPC.
Citation Format: Harshad R. Kulkarni, Thomas Langbein, C Atay, Aviral Singh, Christiane Schuchardt, Coline Lehmann, Martin Pomper, Kenneth J. Pienta, Richard P. Baum. Safety and long-term efficacy of radioligand therapy using Lu-177 labeled PSMA ligands in metastatic prostate cancer: A single center experience over 5 years [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT015.