Exploring the Potential of Lutetium PSMA in High-Risk Localized Prostate Cancer: The LuTectomy Trial - Renu Eapen

November 23, 2022

Renu Eapen, a recipient of the PCF Young Investigator Award, details her groundbreaking project on early use of Lutetium PSMA for high-risk localized prostate cancer. The two-cohort clinical trial involves administering Lutetium PSMA upfront, followed by radical prostatectomy. An integral part of the study is the translational work, analyzing changes in the tumor microenvironment in response to Lutetium PSMA. Dr. Eapen is uniquely positioned to compare pre- and post-treatment tissue samples, shedding light on gene profiling, immune cell subsets, and potential clonal dominance. She reveals that recruitment for the two and a half year-long trial has been completed, with promising preliminary results already presented at the EAU. Looking forward, Dr. Eapen is keen to investigate the potential of Lutetium PSMA in combination with other treatments, to answer critical questions and design future trials, such as LuTectomy II.

Biographies:

Renu Eapen, MBBS, FRACS (Urol), Consultant Urologist, Genitourinary Oncology Service, Peter MacCallum Cancer Centre, Melbourne, Australia, Olivia Newton-John Cancer Centre-Austin Health, Heidelberg, Victoria, Australia

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts


Read the Full Video Transcript

Alicia Morgans: Hi. I'm so excited to be here at the Prostate Cancer Foundation 2022 Annual Summit, where I am here with Dr. Renu Eapen, who is a urologist and a surgeon scientist who was awarded a PCF Young Investigator Award. So, excited to talk to you about that today, and congratulations.

Renu Eapen: Thank you so much, Alicia, and thank you so much for having me. It's wonderful to be here.

Alicia Morgans: It is wonderful to have you, and really to feel your enthusiasm, to hear about your project. Tell us what you were just awarded. What is your project?

Renu Eapen: So, yeah, it's a very exciting project that we've got happening at Peter Mac. It's looking at the early use of Lutetium PSMA. We are very passionate about PSMA Theranostics back home, and this is one of the earliest users of Lutetium PSMA. We're using it in an upfront setting for high risk localized prostate cancer. So, we are giving these patients Lutetium PSMA upfront, followed by a radical prostatectomy. So, we've divided them into two cohorts, cohort A and cohort B. Cohort A gets one dose of Lutetium PSMA followed six weeks later by surgery. And then cohort B gets two doses spaced six weeks apart, and then followed six weeks later by surgery. So, that's a clinical part of the trial. And it's very exciting. But we're only using two doses of Lutetium PSMA. So, although it'll be very interesting to see what the oncological effects are, we're not expecting that all the cancer will melt away.

But I think one of the most interesting aspects of it is the translational work, and that was what my award was for. And the translational work is really looking at the changes in the tumor microenvironment in response to Lutetium PSMA. So, we're in a very lucky position because we've got access to this wonderful tissue where we've got the biopsy pre-Lutetium treatment, and then we've got the radical prostatectomy tissue post-Lutetium treatment. And we're able to do some amazing experiments to see what happens to the microenvironment, what happens to the immune cell subsets, do some gene profiling, and look at T-cells within the tumor microenvironment and in the peripheral circulation and see if there's clonal dominance. So, it's exciting, and it'll be very exciting to see what happens over the next three years and beyond.

Alicia Morgans: Well, absolutely. And to your point, the opportunity to really investigate when you have tissue samples and you have clinical data, this is so important. And where do things stand? I know the LuTectomy Trial has been ongoing. Have you finished enrollment? Where does this stand?

Renu Eapen: Yeah. So, it's been going on now for about two and a half years, and we've just finished recruiting the 20 patients. So, patient 20 underwent his radical prostatectomy a couple of months ago. So, we presented the results of cohort A at EAU, our co-PI of trial, Declan Murphy presented that at the Practice Changing Plenary session at EAU, and it was very well received. And I will, hopefully, be presenting the entire cohort A and B and the comparisons at ASCO GU next year.

Alicia Morgans: Wonderful. Well, great. So, what are the milestones you're most excited to meet over the next few years of this award?

Renu Eapen: I mean, the translational work is going to be really interesting, and I think it'll be really interesting to see what Lutetium does to prostate cancer. And we've always had this perception that all prostate cancers are immunologically cold. But as we've heard at this scientific retreat, that's not true. And that's what we've seen in the preliminary work that we've done, as well. There are some tumors that are actually hot, and they remain hot after a Lutetium PSMA treatment. We're seeing very heterogeneous results. So, it'll be very interesting to combine the 20 patients and see what we can find.

So, that's more the immediate future goals. I think, beyond all of this, it'll be very interesting to see Lutetium PSMA in combination with other treatments. And I think the translational work that we do now will help us to answer a lot of questions and design those future trials. And I think it'll be very interesting, also, to design LuTectomy II. That's our next main goal, and we'll have to just see how that's going to shape up. And I think the PCF award will be an amazing support to making that all happen over the next three to five years.

Alicia Morgans: Well, I could not agree more. And I really look forward to seeing where this goes. I think there's a world out there that is really excited to not only see the clinical data from LuTectomy, but to your point, to really understand the basic biology of what's happening, especially in these patients with very early disease and probably patients who do not have metastatic disease, don't have bone marrow involvement. Patients in a whole different space, and you are going to provide that information. So, keep up the good work. Please keep us posted, and thank you so much for your time today.

Renu Eapen: Thank you so much, Alicia, and you are today.