First Patient Treated with Pluvicto™ in Pre-Chemotherapy Setting Following FDA Approval - Steven Finkelstein
April 4, 2025
Zachary Klaassen speaks with Steven Finkelstein about the FDA approval of Pluvicto™ (177Lu-PSMA-617) in the pre-chemotherapy setting for metastatic castration-resistant prostate cancer. Dr. Finkelstein discusses his team's achievement of treating the first U.S. patient under this new indication just six days after the March 28, 2025 approval. He highlights results from the PSMAfore trial showing Pluvicto™ reduced progression or death risk by 59% compared to changing ARPI therapy, more than doubling median radiographic progression-free survival from 5.6 to 11.6 months. Dr. Finkelstein predicts this approval will create a "tidal wave" of radioligand therapy moving upstream before chemotherapy, potentially tripling the eligible patient population. He emphasizes the favorable safety profile with predominantly grade 1-2 side effects and the significance of offering effective therapies earlier, as approximately half of mCRPC patients don't live long enough to receive second-line treatments.
Biographies:
Steven Finkelstein, MD, DABR, FACRO, National Director of Radiation Oncology, U.S. Urology Partners, Director of the Center of Advanced Radiation Excellence (CARE), Director of Radiation Oncology Research, AMP Syracuse, NY
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Steven Finkelstein, MD, DABR, FACRO, National Director of Radiation Oncology, U.S. Urology Partners, Director of the Center of Advanced Radiation Excellence (CARE), Director of Radiation Oncology Research, AMP Syracuse, NY
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Related Content:
FDA Approves Novartis Radioligand Therapy Pluvicto® for Earlier Use Before Chemotherapy in PSMA-Positive Metastatic Castration-Resistant Prostate Cancer
FDA Approval of 177Lu-PSMA-617 for Taxane-Naive mCRPC - Oliver Sartor
AUA 2024: Paradigm-Shifting, Practice-Changing Clinical Trials in Urology: PSMAfore: Efficacy of 177Lu-PSMA-617 Versus ARPI Change in Taxane-Naïve Patients with Metastatic Castration-Resistant Prostate Cancer by Pre-Randomization ARPI
ESMO 2023: PSMAfore Phase 3 Trial of [177Lu]Lu-PSMA-617 in Taxane-Naive Patients with Metastatic Castration Resistant Prostate Cancer
FDA Approves Novartis Radioligand Therapy Pluvicto® for Earlier Use Before Chemotherapy in PSMA-Positive Metastatic Castration-Resistant Prostate Cancer
FDA Approval of 177Lu-PSMA-617 for Taxane-Naive mCRPC - Oliver Sartor
AUA 2024: Paradigm-Shifting, Practice-Changing Clinical Trials in Urology: PSMAfore: Efficacy of 177Lu-PSMA-617 Versus ARPI Change in Taxane-Naïve Patients with Metastatic Castration-Resistant Prostate Cancer by Pre-Randomization ARPI
ESMO 2023: PSMAfore Phase 3 Trial of [177Lu]Lu-PSMA-617 in Taxane-Naive Patients with Metastatic Castration Resistant Prostate Cancer
Read the Full Video Transcript
Zachary Klaassen: Hi, my name is Zach Klaassen, Urologic Oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on UroToday by Dr. Steven Finkelstein, who is a radiation oncologist in Syracuse, New York. Steven, thanks so much for joining us on UroToday.
Steven Finkelstein: Thank you so much for having me.
Zachary Klaassen: So we're going to talk today. We're going to get into the PSMAfore discussion, the approval of lutetium pre-chemo. I know you guys treated the first patient today in the United States. Before we jump into that discussion, I just want you to give us a little background on your Pluvicto program and how many patients to date you guys have treated up in New York.
Steven Finkelstein: Yeah, so as you know, my background is I'm the National Director of Radiation Oncology for US Urology Partners. I moved up there about six months ago to Syracuse to AMP. And previously, I was with US Oncology in Florida, where we were active in doing Pluvicto on research, was one of the larger accruers to PSMAddition. And I'm six months into our new program here at US Urology Partners.
Zachary Klaassen: Great. And to think we had phenomenal news March 28, 2025. The FDA approved Pluvicto, chemo-naive, so really that second line in mCRPC. So maybe just take our listeners through a very high-level overview of PSMAfore, what really led to the approval in this disease space.
Steven Finkelstein: So with respect to the seminal phase III PSMAfore trial, in this study, Pluvicto reduced the risk of radiographic progression or death by 59% with a hazard ratio of 0.41 and a 95% confidence interval of 0.29, compared to a change in ARPI in patients with PSMA-positive metastatic castration-resistant prostate cancer after treatment with an ARPI therapy. Additionally, in an updated exploratory analysis, Pluvicto more than doubled median radiographic progression-free survival, going from 5.6 months to 11.6 months.
Zachary Klaassen: Yeah, absolutely. So really, really exciting news on that part. And I think when we look at the denominator in that third line versus what really is now the second line, this is really going to open it up for a lot of patients to be candidates. And as I mentioned at the top, you guys were the first group to treat somebody in this new FDA-approved setting. How did things go today? Tell us a little bit about today.
Steven Finkelstein: Yeah, today was super-fantastic. We had a patient who had been really, really hoping to get treated in the pre-chemotherapy space. At 1:30 on Friday, we heard that the FDA appropriately had approved this agent in the setting of the pre-chemotherapy space and was able to facilitate getting the dose to us by Wednesday and delivering it at 8 o'clock this morning. And as you know, I think the patient was extremely excited to go from not being able to get this agent to, within six days, getting it here at AMP at US Urology Partners.
Zachary Klaassen: Yeah, that's super-exciting. And you kind of lead into my next question: really, the feedback from the patient must be ecstatic, to be able to do this before chemo. Any other takeaways from just the patient experience today?
Steven Finkelstein: Yeah, I think the patient and his family had a really good patient experience. I'm hopeful that the side effect profile will reflect the PSMAfore data. And as we know, it had a consistent and favorable safety profile within the PSMAfore trial. The most frequently reported adverse events on the trial were predominantly grade 1 to 2, included some dry mouth in about 61% of patients, some fatigue in 53% of patients, nausea in 32% of patients, and constipation in about 22% of patients. So we're hoping that this really provides a real good benefit for this patient. And I think he and his family were so excited that he could be one who could get the therapy only six days after its approval by the FDA.
Zachary Klaassen: Yeah, absolutely. And I think, just to look at a high-level view as we look in the weeks and months post-FDA approval, and as I mentioned, the denominator is going to be a lot bigger for availability of patients being candidates for Pluvicto. How do you see this changing treatment sequencing in that mCRPC space? It's kind of the golden—we want to figure out exactly what order to do these treatments. How do you see it in your practice?
Steven Finkelstein: I really think that this is going to allow RLT to be moved upstream. In fact, I think it's going to be a tidal wave of seeing a move where patients get radioligand therapies before chemotherapy in a way that we have never seen before. So it's an exciting time in the field, exciting time to be a radiation oncologist, to be able to help our patients in this way.
Zachary Klaassen: Yeah, no question. Great discussion, and congratulations for the first treatment. And like I said, I hope your patient does well, and the ones that come downstream of that. Any summary points, anything you want to hit on that we haven't hit on, and maybe a couple of takeaway messages for our listeners?
Steven Finkelstein: My takeaway: three key points. Approximately half of metastatic castration-resistant patients do not live long enough to receive a second treatment, and that highlights the need for earlier use of effective therapies that have a demonstrated tolerability. Pluvicto significantly reduced the risk of progression or death by 59% and more than doubled median radiographic progression-free survival versus a change in ARPI in that seminal PSMAfore trial. Lastly, this new indication probably triples eligible patients, allowing Pluvicto to be used after one androgen receptor pathway inhibitor and now before chemotherapy.
It's really a pleasure talking with you today about this. I think it's a really exciting time to help our patients with prostate cancer.
Zachary Klaassen: Yeah, well said, Steve. And congratulations again to you and your team for joining us on the same day that the first patient was treated in the United States. So thanks again for your time.
Steven Finkelstein: Thank you so much for having me.
Zachary Klaassen: Hi, my name is Zach Klaassen, Urologic Oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on UroToday by Dr. Steven Finkelstein, who is a radiation oncologist in Syracuse, New York. Steven, thanks so much for joining us on UroToday.
Steven Finkelstein: Thank you so much for having me.
Zachary Klaassen: So we're going to talk today. We're going to get into the PSMAfore discussion, the approval of lutetium pre-chemo. I know you guys treated the first patient today in the United States. Before we jump into that discussion, I just want you to give us a little background on your Pluvicto program and how many patients to date you guys have treated up in New York.
Steven Finkelstein: Yeah, so as you know, my background is I'm the National Director of Radiation Oncology for US Urology Partners. I moved up there about six months ago to Syracuse to AMP. And previously, I was with US Oncology in Florida, where we were active in doing Pluvicto on research, was one of the larger accruers to PSMAddition. And I'm six months into our new program here at US Urology Partners.
Zachary Klaassen: Great. And to think we had phenomenal news March 28, 2025. The FDA approved Pluvicto, chemo-naive, so really that second line in mCRPC. So maybe just take our listeners through a very high-level overview of PSMAfore, what really led to the approval in this disease space.
Steven Finkelstein: So with respect to the seminal phase III PSMAfore trial, in this study, Pluvicto reduced the risk of radiographic progression or death by 59% with a hazard ratio of 0.41 and a 95% confidence interval of 0.29, compared to a change in ARPI in patients with PSMA-positive metastatic castration-resistant prostate cancer after treatment with an ARPI therapy. Additionally, in an updated exploratory analysis, Pluvicto more than doubled median radiographic progression-free survival, going from 5.6 months to 11.6 months.
Zachary Klaassen: Yeah, absolutely. So really, really exciting news on that part. And I think when we look at the denominator in that third line versus what really is now the second line, this is really going to open it up for a lot of patients to be candidates. And as I mentioned at the top, you guys were the first group to treat somebody in this new FDA-approved setting. How did things go today? Tell us a little bit about today.
Steven Finkelstein: Yeah, today was super-fantastic. We had a patient who had been really, really hoping to get treated in the pre-chemotherapy space. At 1:30 on Friday, we heard that the FDA appropriately had approved this agent in the setting of the pre-chemotherapy space and was able to facilitate getting the dose to us by Wednesday and delivering it at 8 o'clock this morning. And as you know, I think the patient was extremely excited to go from not being able to get this agent to, within six days, getting it here at AMP at US Urology Partners.
Zachary Klaassen: Yeah, that's super-exciting. And you kind of lead into my next question: really, the feedback from the patient must be ecstatic, to be able to do this before chemo. Any other takeaways from just the patient experience today?
Steven Finkelstein: Yeah, I think the patient and his family had a really good patient experience. I'm hopeful that the side effect profile will reflect the PSMAfore data. And as we know, it had a consistent and favorable safety profile within the PSMAfore trial. The most frequently reported adverse events on the trial were predominantly grade 1 to 2, included some dry mouth in about 61% of patients, some fatigue in 53% of patients, nausea in 32% of patients, and constipation in about 22% of patients. So we're hoping that this really provides a real good benefit for this patient. And I think he and his family were so excited that he could be one who could get the therapy only six days after its approval by the FDA.
Zachary Klaassen: Yeah, absolutely. And I think, just to look at a high-level view as we look in the weeks and months post-FDA approval, and as I mentioned, the denominator is going to be a lot bigger for availability of patients being candidates for Pluvicto. How do you see this changing treatment sequencing in that mCRPC space? It's kind of the golden—we want to figure out exactly what order to do these treatments. How do you see it in your practice?
Steven Finkelstein: I really think that this is going to allow RLT to be moved upstream. In fact, I think it's going to be a tidal wave of seeing a move where patients get radioligand therapies before chemotherapy in a way that we have never seen before. So it's an exciting time in the field, exciting time to be a radiation oncologist, to be able to help our patients in this way.
Zachary Klaassen: Yeah, no question. Great discussion, and congratulations for the first treatment. And like I said, I hope your patient does well, and the ones that come downstream of that. Any summary points, anything you want to hit on that we haven't hit on, and maybe a couple of takeaway messages for our listeners?
Steven Finkelstein: My takeaway: three key points. Approximately half of metastatic castration-resistant patients do not live long enough to receive a second treatment, and that highlights the need for earlier use of effective therapies that have a demonstrated tolerability. Pluvicto significantly reduced the risk of progression or death by 59% and more than doubled median radiographic progression-free survival versus a change in ARPI in that seminal PSMAfore trial. Lastly, this new indication probably triples eligible patients, allowing Pluvicto to be used after one androgen receptor pathway inhibitor and now before chemotherapy.
It's really a pleasure talking with you today about this. I think it's a really exciting time to help our patients with prostate cancer.
Zachary Klaassen: Yeah, well said, Steve. And congratulations again to you and your team for joining us on the same day that the first patient was treated in the United States. So thanks again for your time.
Steven Finkelstein: Thank you so much for having me.