Apalutamide in Patients with mCSPC: Background
Neeraj Agarwal, MD, and Simon Chowdhury, MD, examine the efficacy and safety data presented in the recent publication, “Apalutamide in Patients with Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study.”
Simon Chowdhury, MD: Hello, and welcome. My name is Simon Chowdhury. I’m a medical oncologist in London, England. Today my close colleague and friend Neeraj Agarwal and I are going to be discussing the recent JCO [Journal of Clinical Oncology] paper looking at the final survival analysis of apalutamide from the TITAN study of men with metastatic castration-sensitive prostate cancer. I’m going to pass it over to Neeraj so he can introduce himself, and then we’ll discuss the paper.
Neeraj Agarwal, MD: Thank you, Simon. I’m glad to be here. I’m looking forward to discussing these updated data from the TITAN trial. For the sake of introduction, I’m a professor of medicine and the director of the genitourinary oncology program at the Huntsman Cancer Institute at University of Utah in Salt Lake City. I’m glad to be here.
Simon Chowdhury, MD: I should have also said that Neeraj is the senior author on the final survival analysis and has been integral in driving this study forward to its successful end point, which we’ll talk about. This is a study of men with metastatic castration-sensitive prostate cancer. Previously, in the New England Journal of Medicine paper, which Neeraj and I were both part of, we saw an improvement in both radiographic and progression-free survival [PFS]. But that was the first interim analysis. This is the final analysis with the updated data that we’re going to discuss. I’m going to move to the next slide. Neeraj, what are your thoughts on the demographics of the patients and the other features here?
Neeraj Agarwal, MD: This slide tells us that most of the patients received life-prolonging therapies after they had disease progression or when they discontinued protocol treatment. This is important because if patients in the placebo arm don’t get life-prolonging therapy after disease progression, that can skew the benefit in favor of the experimental arm. First, I’d like to bring your attention to the fact that 40% of patients on the placebo arm—which we’ll be discussing in next 2 or 3 slides—crossed over to receive apalutamide at the time of the first interim analysis. After it was shown that overall survival was present and the trial met the dual primary end points of radiographic PFS and overall survival, those 40% of placebo patients—a pretty good number—were crossed over to receive apalutamide.
If you look at the right box on this slide, 138 patients in the apalutamide arm and 261 patients in placebo arm discontinued treatment for progressive disease and remained alive. Of these patients, the vast majority—almost 70% patients—received subsequent life-prolonging therapies. Based on these data, I can assume without a doubt that this was a representation of what we do in our clinics. The majority of patients receive subsequent therapy after they progress on treatment given in the hormone-sensitive metastatic prostate cancer setting.
Simon Chowdhury, MD: That’s a brilliant summary. We’re going to talk about some of the innovative work that’s been done from this study, led by Neeraj and looking at PFS2, progression-free survival 2. It ties into the things that Neeraj has brought up there because ADT [androgen deprivation therapy] is very active but isn’t active enough. Apalutamide is a very active drug, but this isn’t 2 active drugs vs 1 active drug without the other 1, which unfortunately happens in some studies. This is a properly conducted study, and the number of patients crossing over is important. We’ll talk about how that probably underestimates the benefit of apalutamide and how we as a steering committee weighted for that.
Transcript edited for clarity.
