"Some of these patients newly referred don't have any other proven therapies remaining...This is the only one on the shelf that has a proven benefit. Unfortunately, we can't offer them that at this stage," says Praful Ravi, MD, BChir, MRCP.
In this interview, Praful Ravi, MD, BChir, MRCP, discusses the current shortage of 177Lu-PSMA-617 (Pluvicto) in the United States. Ravi is a medical oncologist at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts.
Pluvicto, or Lutetium-PSMA-617, was approved in March 2022, so a year ago now, on the basis of the positive VISION trial1 (NCT03511664), which showed a significant benefit in overall survival in men with hormone-resistant prostate cancer after at least 1 line of chemotherapy and 1 normal hormone agent. It's really another tool in the toolbox. It's added to our therapeutic armamentarium. It's provided another proven life-prolonging option to patients with advanced prostate cancer. It has certainly been a valuable addition, because we only have a finite number of therapies for this disease in this advanced state, and the more treatments we have, likely, the better the outcomes will be.
I don't know if I can fully explain the reasons, because some of them are beyond my area of knowledge or expertise. But I mean, in simplistic terms, I think it's supply and demand. There have been supply issues with getting the drug manufactured, from what I understand, with the company Novartis. There's been a lot more demand for it than perhaps was anticipated. So predominantly, I believe we're limited by the supply, but I think the demand has been much higher than expected. That, in simple terms, is leading to this shortage.
In terms of patient care, the shortage obviously [affects] clinical decision-making. We have patients who are eligible for Lutetium per the FDA label and per the VISION criteria and meeting the trial requirements and eligibility, but unfortunately, we're not able to start them on treatment. The shortage is currently predominantly affecting new patients, patients newly referred for this treatment, or potentially eligible. Existing patients who have already started their treatment are generally being on the whole, less affected, although some have still been affected in terms of delays, but it's really the new patients. Some of these patients newly referred don't have any other proven therapies remaining. All other therapies have failed them. This is the only one on the shelf that has a proven benefit. Unfortunately, we can't offer them that at this stage.
So clearly, we're trying to think about what can we do? Are there alternatives? Some people, they may have other alternatives. I think it's very important for the community to realize that [although] the label for Lutetium is having just had 1 prior chemotherapy and 1 prior novel hormone agent, there are other chemotherapies and hormone agents and other classes of therapy, including, for example, radium, which are available, as well, which all have a proven benefit in terms of prolonging life. So, where it's feasible, and where the patients are eligible, I and others are trying to use alternative therapies, which have probably a similar impact in terms of improving longevity of life for patients. It's really for those patients who've been through everything, and we don't have anything else left. They're the ones really impacted.
I'll also say clinical trials are a big thing. [Although] not all trials are beneficial for everyone, some patients do benefit from trial drugs, from experimental drugs. We're always trying to look out for clinical trials that someone might be eligible for. It's really all about sequencing and buying time and adding each agent, adding a little bit of time. If you string all those out, then you can make that time longer. It's really trying to think about alternatives, trying to think about clinical trials, trying to think what else have they been through? What have they been through in the past? Can we use similar or the same drugs again? And really, that's how we decide how we are managing this in clinic.
I, along with countless others have experienced this. Patients, for example, who are newly due to begin this month, in fact, this week have been delayed and canceled at the last minute saying that you’re not going to begin until 2 to 3 weeks, or even longer, so we're like, well, should we do something else in the meantime? The disease is growing. We have an idea but perhaps it's not completely clear when it's going to start this Lutetium treatment for them. We have to think, well, should we give them maybe some more chemotherapy or a different treatment? It's making us change plan or change course.
I feel very sorry for patients who have been given this date and have geared themselves up for starting this treatment, because this treatment is not a pill or not even a chemotherapy; it's a radioactive treatment, which has associated precautions and things they have to take. They have to re-adjust their life to some degree around it in terms of avoiding contact with close relatives or pregnant women and children. It wreaks havoc to their life schedule on occasion. We, as clinicians, have to be nimble and think about, well, do we need to do something else in the meantime? Do we perhaps think about clinical trials? Should we think about a new treatment? Should we keep them going a little bit longer on their chemotherapy? It has forced us to have tough conversations for patients who don't have that time and to think about what's most important to them if, for example, we're not able to get them to this treatment.
I think we all just have to rewind back a year ago. Lutetium was not available. It was not approved. We did not have it as a standard-of-care option, and we had the other treatments. It's important not to lose sight of that. Yes, it is a proven life-prolonging therapy, and yes, it is very exciting. It's sort of a personalized therapy, because it's based on your PSA expression on a PET scan. But we have other proven therapies available. And it's sometimes easy to be blinded by the potential luster of this treatment as a new treatment, and everyone's very excited by it. Let's not lose track that we have other treatments that have, in trials, arguably shown similar benefit in a similar population. We have still those available. We have clinical trials available. I would say that those are the 2 big things we need to look at, at least the patients who have those options left. For patients who don't, it's very hard and not much that we can do in terms of conjuring up a new therapy, but at least we can try and think about other therapies we have available and clinical trials. Those are the 2 big messages.
1. Morris MJ, De Bono JS, Chi KN, et al. Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). J Clin Oncol 39, 2021 (suppl 15; abstr LBA4).