clinical topic updates

Prostate-Specific Membrane Antigen–Targeted Radioligand Therapy for Advanced Prostate Cancer

by Oliver Sartor, MD

Overview

Prostate-specific membrane antigen (PSMA)–targeted radioligand therapy has the potential to be practice changing. Featured expert Oliver Sartor, MD, provides his insights on the VISION study of lutetium-177 (177Lu)–PSMA-617 in men with metastatic castration-resistant prostate cancer (mCRPC).

Expert Commentary

Oliver Sartor, MD

C. E. and Bernadine Laborde Professor of Cancer Research
Medical Director, Tulane Cancer Center
Associate Dean for Oncology
Tulane University School of Medicine
New Orleans, LA

“Not only do we have the initial positive results from the VISION trial with regard to OS benefits and how well the therapy is tolerated but we are also going to have new trials launching into earlier spaces, which will be a very important opportunity for progress in this patient population.”

Oliver Sartor, MD

Earlier this year, a press release reported that the VISION study met both primary end points, significantly improving overall survival (OS) and radiographic progression-free survival in patients with PSMA-positive mCRPC. More recently, we had the honor of presenting some of the preliminary data from the VISION trial at the recent 2021 American Society of Clinical Oncology Annual Meeting. 

Suffice it to say, this prospective, randomized, phase 3 trial is pivotal for 177Lu-PSMA-617 and clearly demonstrates an improvement in OS, with a substantial reduction in the risk of death for those individuals who received standard of care plus 177Lu-PSMA-617. In addition, the data strongly indicate that this new radiopharmaceutical therapy is well tolerated. And this combination of improvements in OS in the context of a well-tolerated therapy is critically important. 

The patients who were treated in the trial had advanced disease and had failed androgen receptor pathway inhibitor therapy (ie, either abiraterone, enzalutamide, or apalutamide) and 1 or 2 taxane therapies. So, this was an extremely difficult-to-treat patient population. 177Lu-PSMA-617 provides an alternative to patients who truly have few alternatives. 

We know from the VISION trial that the presence of metastatic lesions having PSMA positron emission tomography avidity that is greater than that of the liver can be used in patient selection. We excluded patients who had lymph nodes greater than 2.5 cm as measured via cross-sectional imaging if they were PSMA negative, and we also excluded PSMA-negative lesions that were greater than 1 cm in visceral organs such as the lung or the liver. So, in terms of patient selection, I think that we have a road map going forward based on the VISION trial for something that we know is effective. Whether that will be potentially refined in the future is uncertain.

That said, 177Lu-PSMA-617 therapy is now going to be moved up in clinical trials examining earlier points in the course of disease. A trial has been announced in the prechemotherapy mCRPC space (ie, individuals who could have had a novel hormone but no prior chemotherapy), and that study will proceed soon. In fact, more than 1 trial is likely to be conducted in that space. 

In addition, the study of 177Lu-PSMA-617 for individuals who have low-volume metastatic hormone-sensitive disease is part of the plan. A phase 3 trial will be conducted in these patients as well. So, not only do we have the initial positive results from the VISION trial with regard to OS benefits and how well the therapy is tolerated but we are also going to have new trials launching into earlier spaces, which will be a very important opportunity for progress in this patient population.

References

Awang ZH, Essler M, Ahmadzadehfar H. Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches. Radiat Oncol. 2018;13(1):98. doi:10.1186/s13014-018-1037-7

ClinicalTrials.gov. Lutetium-177-PSMA-617 in low volume metastatic prostate cancer. Accessed June 24, 2021. https://clinicaltrials.gov/ct2/show/NCT03828838

Lawal IO, Bruchertseifer F, Vorster M, Morgenstern A, Sathekge MM. Prostate-specific membrane antigen–targeted endoradiotherapy in metastatic prostate cancer. Curr Opin Urol. 2020;30(1):98-105. doi:10.1097/MOU.0000000000000685

Morris MJ, De Bono JS, Chi KN, et al; VISION Trial Investigators. Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION) [abstract LBA4]. J Clin Oncol. 2021;39(suppl 18):LBA4. doi:10.1200/JCO.2021.39.15_suppl.LBA4

Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer. News release. Novartis. March 23, 2021. Accessed June 24, 2021. https://www.novartis.com/news/media-releases/novartis-announces-positive-result-phase-iii-study-radioligand-therapy-177lu-psma-617-patients-advanced-prostate-cancer

Sartor O, de Bono J, Chi KN, et al; VISION Investigators. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021 Jun 23. doi:10.1056/NEJMoa2107322

Yadav MP, Ballal S, Sahoo RK, Dwivedi SN, Bal C. Radioligand therapy with 177Lu-PSMA for metastatic castration-resistant prostate cancer: a systematic review and meta-analysis. AJR Am J Roentgenol. 2019;213(2):275-285. doi:10.2214/AJR.18.20845

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