The Efficacy and Safety of Relugolix versus Leuprolide in the HERO Study in Men with Advanced Prostate Cancer Based on Baseline BMI - Fred Saad
July 25, 2022
Fred Saad, MD, FRCS, Professor and Chief of Urology, Director of GU Oncology, Raymond Garneau Chair in Prostate Cancer, University of Montreal Hospital Centre (CHUM), Director, Prostate Cancer Research, Institut du cancer de Montréal/CRCHUM
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
ASCO 2022: Efficacy and Safety of Relugolix in Men with Advanced Prostate Cancer Based on Baseline BMI: A Subgroup Analysis from the Randomized, Phase 3 HERO Study Versus Leuprolide
EAU 2022: Sustained Castration to 20 ng/dl for Relugolix vs. Leuprolide in Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study
Alicia Morgans: Hi. I'm excited to be at ASCO 2022, where I have the opportunity to speak with Professor Fred Saad, about an analysis in the HERO data. Thank you so much for being here.
Fred Saad: It's a pleasure.
Alicia Morgans: Wonderful. So you and I know that the HERO data is a phase three trial that looked at Relugolix in patients who were going to be getting a year of androgen deprivation therapy in comparison to Leuprolide. Primary endpoint here, of course, is rate of patients who became castrated or had castrate levels of testosterone and continued to have that castrate level of testosterone. But this is a really rich data set, and we can ask so many questions within it. You and the team looked at how BMI might affect your efficacy of Relugolix in the population, of course, important because this is an oral agent. So, can you tell me a little bit about the work that you presented?
Fred Saad: Yeah. So, what we did was look at Relugolix compared to Leuprolide in patients with different BMIs. And, obviously, that is the realities that we have patients that are very thin, patients that are quite obese. And so, it was a concern. Is it a different metabolism? And it was very reassuring that the bottom line is irregardless of BMI, the efficacy of Relugolix made no difference in terms of the speed of testosterone decline. The persistence of decline in testosterone was extremely well and surpassed what was seen with Leuprolide. Even though in Leuprolide, it was always given the way it should have been given. There wasn't any benefit of Leuprolide over Relugolix, which is an oral antagonist, which could have been affected by BMI and weight of the patient. So, quite reassuring that we don't need to adjust doses based on BMI. We can maintain the same dose that we use across the board for patients that need ADT for treating their prostate cancer.
Alicia Morgans: I think that's such an important and interesting concept. As an oral agent, this is, of course, a standard dose that you get once daily. But in many of our oncology therapies, we base the dosing on milligrams per meter squared or really using a body surface area type approach to dosing these agents. And so, someone's weight absolutely will affect the dose of the drug that this individual gets. So, so important that you and the team looked at this because there could be, and there are in certain agents that we use for treating cancer, there are differences by BMI.
Fred Saad: Right. BMI. We looked at age. We looked at toxicity. And so this was all very reassuring that pretty standard, and if we need a rapid mechanism of action from an antagonist with the theoretical possible benefits in terms of cardiovascular safety, then I think it's something that really should be, and could be considered.
Alicia Morgans: So did you and the team look into or find any differences in things like adverse events based on BMI in this particular trial?
Fred Saad: No. No difference in adverse events. Whereas in other oral agents that we use age and BMI sometimes do affect adverse events. And we know some of the novel hormonals might be affected by patients that are extremely thin, elderly. But we didn't see this with the Relugolix.
Alicia Morgans: Perfect. So, if you had to give a message, it sounds like it's a pretty clear one. What would that message be?
Fred Saad: That if we're going to need an antagonist, especially an oral antagonist, like Relugolix, that we don't have to be concerned about weight, BMI. That we could be reassured that the dose that is established is the adequate dose for our patients.
Alicia Morgans: It's both an adequate and a safe dose for our patients. Really important information as we're trying to unroll this therapy in our clinical practices. Thank you so much for sharing this with us.
Fred Saad: Always a pleasure.