ASCO 2018: Lutetium-177 PSMA617 Theranostics In Metastatic Castrate-Resistant Prostate Cancer: Interim Results of a Phase II Trial

Chicago, IL (UroToday.com)  Lutetium-177 (177Lu)-PSMA617 (LuPSMA) is a small radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody which combines the precision of monoclonal antibodies with the anti-tumor effects of β radiation1. Prostate-specific membrane antigen (PSMA), also known as folate hydrolase I,  is restricted to the prostate membrane and overexpressed 100-1000 times in prostate cancer, and can be detected with RT-PCR assays in the blood, suggesting that this may be a marker of micro-metastatic disease2,3.  Lutetium-177 emits a very short range β particle as well as γ emission – this benefit allows for a lower dose of radiation exposure to the bone marrow which may help it be more tolerable with respect to myelotoxicity. The γ emission allows Lutetium-177 to be used as an imaging agent.

In a single center, phase II study published earlier this year, men with metastatic castration-resistant prostate cancer with confirmed high PSMA-expression on a screening PSMA scan were given four cycles of [¹⁷⁷Lu]-PSMA-617, at six weekly intervals3. The primary endpoint was PSA response. 30 (70%) of 43 patients screened were eligible for therapy. Almost all patients at least one prior line of chemotherapy (80% docetaxel and 47% cabazitaxel) as well as abiraterone, enzalutamide, or both (83%). This early phase II study showed high response rates (82%) with a very favorable AE profile. The most common grade 3 AE was lymphopenia (37%), followed by anemia (13%), thrombocytopenia (10%), neutropenia (7%), and pain (3%). 

UroToday ASCO2018 Lutetium 177 mCRPC

In this updated abstract, 50 patients have been enrolled with a median age of 71. Median PSA was 189.8. Most patients were ECOG 1 (44%) or 2 (16%). This final population was heavily pretreated (see table below). With the additional patients, AE profile remained consistent. Almost every patient had a PSA response with the majority of patients (62%) having >50% PSA decrease from baseline. At this time, median overall survival was 13.4 months. This is similar to the overall survival benefit documented in ALSYMPCA for radium-2234. However, that was a very different population without any visceral disease. 

In Germany, Heck and colleagues have reported similar success in a retrospective report of 100 consecutive patients treated with 177Lu-PSMA, with a median PSA-PFS of 3.4 months and median OS of 12.2 months5.

The compelling objective responses in this phase II study have led to a phase III clinical trial, VISION, which will compare patients receiving Lu-PSMA-617 plus best supportive care alone or in combination with a novel androgen axis drug compared to best supportive care alone. Another trial, ANZUP/PCFA TheraP trial will compare Lu-PSMA-617 with cabazitaxel.

One limitation of this therapy is the ability for widespread use for all patients, as patients with FDG positive sites that are without high PSMA expression were excluded. For future studies, it may be interesting to examine the role of Lu-PSMA-617 in that subpopulation to see if benefit still exists. 

References:
1. Tagawa ST, Milowsky MI, Morris M, et al. Phase II Study of Lutetium-177–Labeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Metastatic Castration-Resistant Prostate Cancer. Clinical Cancer Research 2013;19:5182-91
2. R. FW, S. IR, D.W. HW. Prostate‐specific membrane antigen. The Prostate 1997;32:140-8
3. Hofman MS, Violet J, Hicks RJ, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. The Lancet Oncology 2018;19:825-33.
4. Parker C, Nilsson S, Heinrich D, et al. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer. New England Journal of Medicine 2013;369:213-23.
5.Heck M, Schwaiger S, Knorr K, et al. Radioligand therapy with Lutetium 177-labeled PSMA-I&T for metastatic castration-resistant prostate cancer: Clinical experience with 100 consecutive patients. European Urology Supplements 2018;17:e874.


Presented by: Shahneen Kaur Sandhu, MD. Department of Medical Oncology, Peter MacCallum Cancer Centre, Australia

Written by: Jason Zhu, MD, Fellow, Division of Hematology and Oncology, Duke University, at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
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