Why lutetium-177–PSMA-617 is highly sought after by patients with mCRPC

Lutetium-177–PSMA-617 is a novel investigational treatment for patients with metastatic castration-resistant prostate cancer, but is it more efficacious than the standard of care for this patient population?

The impact of the VISION trial, a study investigating prostate-specific membrane antigen (PSMA)-targeted therapy for advanced prostate cancer, was discussed in a talk presented by Michael J. Morris, MD, at the 2021 Society of Urologic Oncology Annual Meeting.¹ In this presentation, he emphasized the favorable results of lutetium 177 from this study and why more and more patients are seeking this treatment option. Morris is the section head of prostate cancer in the GU oncology service at the Memorial Sloan Kettering Cancer Center in New York, New York.

Can you briefly discuss the background and findings of the VISION trial?

The VISION trial is a randomized, phase 3 study, which tests the clinical benefit of a radiopharmaceutical called lutetium 177 PSMA 617.² [This] is a PSMA-directed small molecule that carries a payload of lutetium 177, a beta emitter. This study is designed to compare a protocol-defined standard of care to that protocol-defined standard of care in combination with lutetium 177 PSMA. These patients have metastatic castration-resistant prostate cancer, [and] they have had to have been treated with at least 1 androgen receptor pathway inhibitor and at least 1 prior chemotherapy. They also had to have had a PSMA PET/CT, which revealed PSMA avid disease. The primary end points were radiographic progression-free survival and overall survival. The study has demonstrated, now presented at 2 separate meetings and [published] in the New England Journal [of Medicine], a 38% survival benefit, a 60% improvement in radiographic progression or death, and a 50% improvement in time to first symptomatic skeletal event. Presented at ESMO were data that showed that it preserved quality of life better than the standard of care did. That is in favor of lutetium, and lutetium also reduced time to first pain. So, it's truly the trifecta of drug development. It improved how patients feel, how they function, and how they survive.

How has or how will PSMA-targeted therapy change the advanced prostate cancer space for both physicians and patients?

I think it will be transformative, certainly for [the] last phases of the disease that the VISION trial population represents, providing that the FDA approves the drug. It introduces a new type of therapy. It's the first tumor-directed radioligand therapy for prostate cancer. It provides a platform for new combinations. But in terms of the advanced disease patient population overall, we have a lot of work to do to define how to optimize the integration of this therapy into what we call 'advanced prostate cancer.' So, this is a very late group of patients that VISION represents. There are earlier metastatic castration-resistant patients who may derive greater benefit from the drug earlier in the disease, and then there's the whole castration-sensitive population as well, who could be candidates for this type of therapy. And there's a phase 3 study that is now open and accruing, intended to look at that. How we define 'advanced' is [also] changing because PSMA imaging is detecting advanced disease much earlier in the natural history than we used to detect with just bone scintigraphy and with standard cross-sectional imaging. Now, we're picking up advanced disease in otherwise non-metastatic CRPC, non-metastatic CSPC, and even locally advanced disease. And I think that we would all like to see whether lutetium has a treatment role to play in improving those patients’ outcomes as well.

Finally, there's a whole question as to how to optimize patient selection. The VISION trial used PSMA imaging with a relatively lax criteria for study entry, but there are other biomarkers—imaging, genetic, and serum biomarkers—that may play a role in better selecting patients to optimize those who are treated with lutetium. So, there are many questions that are [still] open that we're exploring to see whether we can better identify who will benefit from [this population of] patients, both in traditional advanced disease and in what will likely be a newly defined advanced patient population.

Are the results of this trial going to affect your own practice? Why or why not?

The results of this trial impacted practice globally. Even without formal FDA approval, this therapy has been available in other countries, and we've seen patients who really want access to this drug leaving this country and going to those countries to be treated. There is an early-access program that has been in patient demand. I think that there's a huge amount of enthusiasm on the part of both clinicians and patients to get this therapy, especially since VISION focused on a patient population with very few treatment options. So, this has already begun to shift the profile of therapeutics that are available for this patient population. And there's that enthusiasm that's there, on the basis of the results of the VISION trial, that have already begun to change how people think about radiopharmaceuticals and prostate cancer to a much more enthusiastic embrace of this approach than we've seen with prior, let's say, bone-seeking radiopharmaceuticals.

References

1. Morris MJ. VISION trial: Integrating PSMA-targeted therapy for advanced prostate cancer. Lecture presented at: 2021 Society of Urologic Oncology Annual Meeting; December 1-3, 2021; Orlando, Florida

2. Sarton O, de Bono J, Chi KM, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322