First PSMA PET Set to Improve Imaging in the Prostate Cancer Field

The F 18-labeled prostate-specific membrane antigen (PSMA)–targeted positron emission tomography (PET) imaging agent 18F-DCFPyL (Pylarify) is the first available PSMA PET imaging agent for prostate cancer.¹

18F-DCFPyL, which works to identify suspected metastasis or recurrence in patients with prostate cancer, was developed to target PSMA. By binding to the target, the reader of the PET scan can detect and locate the disease.

18F-DCFPyL was approved by the FDA back in May 2021 based on data from 2 studies, which were designed to look at the safety and diagnostic performance of 18F-DCFPyL across various types of prostate cancer. First the phase 2/3 OSPREY study (NCT02981368) found that the agent has a high positive predictive value in prostate cancer.² Second the phase 3 CONDOR study (NCT03739684) showed that provided clinically meaningful and actionable information in patients with suspected recurrence of prostate cancer.³

In an interview with Targeted OncologyTM, Bridget Koontz, MD, United States (US) chief medical officer and deputy global chief medical officer at GenesisCare, discusses 18F-DCFPyL and how the well-tolerated agent can change the way prostate cancer patients are treated.

Can you provide a brief overview of what 18F-DCFPyL is?

Koontz: Pylarify is an F 18-DCFPyL, which is a PSMA PET. Pylarify specifically is a radionuclide tracer. It targets the extracellular PSMA component to visualize prostate cancer cells anywhere in the body. It is very specific to the prostate as very few organs exhibit PSMA. The biggest one that can be an issue is the salivary glands, but it helps to let us identify where prostate cancer cells are, particularly in the setting of whether we have a high patient who's just been diagnosed and we're concerned that they might have metastatic disease or a patient whose PSA is rising and we know they have recurrent disease and are trying to figure out where. Doing a PSMA PET can help us find where that is, and then we can better target its treatment.

I think of radiation therapy which is a type of focal therapy or targeted therapy to an anatomical region. We sometimes have to guess where we think the cancer is, and the best example of that is if we have breast cancer. Not only do we treat the tumor in the breast, we, [but we also] frequently treat the whole breast because there's a tumor that we see, and then there's a tumor that we don't see that we need to include in the radiation field. Sometimes we do guess where we think the cancer might be, but every time we do that, we have to use best evidence, estimates of what follow up series, where has the cancer recur, what is the likelihood that it's in the lymph nodes. There are lots of ways of estimating the chances of where cancer might be and then we balance the risk of treating that area versus the potential benefit where if we're right, that's where the cancer is.

Better imaging so that we can see the tumor allows us to be more accurate in our determination of where we need to treat, which allows us to increase the efficacy of our treatments, and decrease the toxicity of our treatments. That's why patients and doctors are so excited about PSMA PET in general and Pylarify as one of the specific tracers, and it's the only FDA approved PSM tracer that I'm aware of in the US at the moment. That really can revolutionize how we can stage patients with prostate cancer and therefore be able to give them the very best counseling on the right treatments.

Can you discuss the role of Pylarify in prostate cancer?

It changes the whole paradigm for how we approach patients who have recurrent or metastatic disease. Before, if someone was diagnosed with metastatic prostate cancer, we would put them on medication that took all of their testosterone away, so we medically castrated these men. Over time, they would need chemotherapy to again suppress the cancer and it's just a long course of testosterone deprivation and chemotherapies that they would go on. In some cases, that is often still needed. But the advantage of PSMA PET testing and Pylarify is that if we can find their disease when it's just starting to metastasize very early in that process, and they only have a few metastases, we can treat them with targeted radiation. In some cases, instead of going on testosterone suppression, we can target those areas with radiation, put them back into remission, and give them several more years.

Can you explain the mechanism of action of 18F-DCFPyL?

PSMA is a transmembrane protein that is present in prostate cells and overrepresented in cancer prostate cancer cells. Pylarify is designed to target that protein and, there were older agents that were in use that targeted the internal intracellular component of PSMA. That was challenging because the compound had to get into the cell before it could bind, so it didn't work very well. But this one binds the extracellular component of the PSMA protein, and the way Pylarify works is that it is attached to a radioisotope that emits protons.

The 18F has a short half-life. It is bound to the Pylarify agent, it is injected into the body, it circulates for a number of minutes and then the patient is put in a scanner. That scanner does a CAT scan, and it does a PET scan. In the process, the radioisotope is bound to the PSMA and then as 18F degrades, because it's radioactive, it emits positrons, and that positron is picked up in the PET scanner and lights up like a light bulb. It's like looking at stars in the sky. You have this very dark image of the body with a little bit of background and then you've got this bright white light where the PSMA tracer agent is attached to prostate cancer cells. As you can imagine, because it's such a bright spot on a dark background, it's very easy to detect small amounts of cancer cells. It's very sensitive, and PSMA PET testing can find prostate cancer, when it has recurred in a patient that doesn't have a prostate, and their PSA is only 0.5 nanograms per milliliter, it can detect recurrence, and sometimes even lower sometimes down to 0.2.

Point 5 is actually very reliable for detecting recurrence, so that's amazing. For a new patient, before we use old techniques like bone scan, or CAT scan, the PSMA frequently was over 10 before we could find their cancer, so it's much more sensitive and then the agent circulates through the body and is usually excreted through the urine. These patients are radioactive very briefly, but not very radioactive, it's a very small dose that's delivered so they're safe to be around. Usually from the injection period to when the scan is done, we keep them in a hot room next to the scanner and once the scan is over, they can go home. They are not a risk to anybody, but they are for a very brief period of time, radioactive from that agent.

What adverse events are associated with 18F-DCFPyL?

It's injected and goes into the bloodstream, and it is very well tolerated. There really aren't any because it's such a low dose. It's similar to a bone scan, it's a minimal dose, so there really aren't any toxicities associated with pylarify itself. The indications in use are for prostate cancer with suspected metastasis or because of high-risk disease or suspected recurrence. The adverse reactions that few patients get are a headache, fatigue, or have a funny taste in their mouth. It is a temporary symptom, and the rate was about 10% for those side effects.

Who was an ideal candidate for 18F-DCFPyL? Which prostate patients subgroups should this agent be used for?

Any man who has been diagnosed with prostate cancer and is felt to have aggressive prostate cancer that has a potential for metastasis. Somebody who has a high grade or a high elevated PSA over 20 are the men who I would say would be candidates. Or any man who has been previously treated with prostate cancer and has been found by PSA testing to have a recurrence would be appropriate. There has been discussion about whether a patient should have a bone scan or a CAT scan, before they have a PSMA PET. There was a guideline that's been published and overall, we felt that for patients who have a very high risk of metastasis, even on conventional imaging, it's probably cheaper to go ahead and do a bone scan, if their PSAs are 100 or more. But for patients who are in the region where it's unlikely that they have bone scan positive disease, a PET scan is much more sensitive so we can find cancer lesions much more effectively and at an earlier stage with pylarify than we would with a bone scan.

Do you think 18F-DCFPyL could be used for other types of solid tumors?

Pylarifyis specific to prostate cancer but I believe that the overall concept is very applicable to other cancers. There are studies being done in agents being developed that will target other cancers like breast cancer, lung cancer, gastrointestinal cancer, so it is coming, but Pylarify is specifically indicated for prostate.

What further information do you want to get from 18F-DCFPyL? What are some of your hopes for the future?

My hope is to be able to cure metastatic prostate cancer, and I think we got a good shot. I have a few men that I think I have cured, but as a field overall, I think as we start to use more of it and have a better understanding of where the disease is, we can do a better job of targeting it. At the very least, get these men back into remission and offer years of hope where they're able to have a good quality of life off of drugs, not needing chemotherapy, and that's a huge win. That is an important message to get across as to what Pylarify and PSMA PET can bring to men with prostate cancer.

The other thing that I think is important to know is for GenesisCare, because we have this history of using PSMA and PET, we really see the importance of it. GenesisCare was the first in the US to use Pylarify. We have multiple PET centers that are being used to help diagnose patients and get them the right therapy that they need. We are also one of the few centers in the US that are starting to use PSMA, targeted treatment where we're actually treating men by targeting the PSM agent with radionuclide therapy. That is very exciting and has been shown to improve overall survival and we are one of the very few sites that are starting to do that. Again, it is an option that eventually needs to get everywhere in the US. With our experience, we were able to initiate that therapy for our patients, and that's something I'm very proud of. I can't wait to see it roll out throughout all of our centers.

References:

1. FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer. FDA website. May 27, 2021. Accessed February 15, 2022. https://bit.ly/3BpF4di

2. Pienta KJ, Gorin MA, Rowe SP, et al. A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18 F-DCFPyL in prostate cancer patients (OSPREY). J Urol. 2021;206(1):52-61 doi: 10.1097/JU.0000000000001698.

3. Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: results from the condor phase III, multicenter study. Clin Cancer Res. 2021;27(13):3674-3682. doi: 10.1158/1078-0432.CCR-20-4573.