ADT Monotherapy in mCSPC

Alicia K. Morgans, MD, MPH: We’ve seen a number of studies in real-world populations that have demonstrated that even in the United States, among medical oncologists, neurologists, and anyone treating these patients, there’s a substantial number of patients with metastatic hormone-sensitive disease, or castration-sensitive disease, who are getting ADT [androgen deprivation therapy] monotherapy alone. I’d love to hear your thoughts on this. I’ll start with Sandy.

But to share my own perspective, we need to think of every patient as getting ADT plus something. Then our second response should be: Is there a reason they can’t get that intensified therapy? And only if they can’t get it, should we back off to ADT monotherapy? Patient preference can be a reasonable reason to use only ADT monotherapy. But that intensification strategy needs to at least be considered. Sandy, what are your thoughts?

Sandy Srinivas, MD: I agree. Alicia, I’m surprised about all these papers that have come out about the real world. You think about practice changing. Nothing in oncology that we’ve seen has resulted in this impactful change in overall survival. If you think about a trial like CHAARTED, to have close to an 18-month difference in overall survival, it’s hard to see it with any other oncology trial we’ve had. That has been consistently shown with not just chemotherapy but abiraterone, enzalutamide, and apalutamide. The NCCN [National Comprehensive Cancer Network] Guidelines have this as a category 1 recommendation, so it’s really surprising to see in the real world that there have been repeated papers saying that fewer than 10% to 15% of patients end up getting either chemotherapy or 1 of these AR [androgen receptor]–targeted drugs. We agree that AR intensification should be the norm, and there should be an absolute reason why they can’t get it. For some of our patients, it may be that these drugs are expensive, or there may be co-payment reimbursement issues.

In my practice, there may be a patient who’s in their 80s—an older patient with multiple, especially cardiac comorbidities—and you may be concerned about what this addition would do. I thought the SWOG-S1216 trial, presented that at this year’s ASCO [American Society of Clinical Oncology Annual Meeting] was intriguing. It was an overall negative trial looking at TAK-700, which is a drug very similar to abiraterone. Overall, the surprising part about that trial was that the standard-of-care arm with just ADT plus bicalutamide outperformed what we’ve seen before, about 70 months, compared with the TAK-700 at 80 months. There may be a small group of patients for whom ADT may be OK. But for the majority today, there is level 1 evidence that ADT intensification, with 1 of these AR-targeted drugs or docetaxel, should be the standard of care. It’s hard to understand why that hasn’t transformed into an adaption.

Alicia K. Morgans, MD, MPH: I agree. SWOG-S1216 was inspiring because it speaks to subsequent therapies being effective and really shifting that survival curve that we saw. But those patients were all in a clinical trial, so my expectation is they probably did get those subsequent therapies, hopefully relatively quickly, at each point of progression, which isn’t always the case in the real world. I always favor earlier intensification unless, as you said, there’s a reason not to. Because if we don’t do it early, we may miss that opportunity to do it ever and certainly miss that massive benefit in terms of survival. Scott, what are your thoughts on this?

Scott T. Tagawa, MD, MS, FACP:I haven’t been able to figure out why at least the 5 days that I know of that have been presented—Medicare data sets, a VA [Veterans Affairs] data set, and 3 commercial internal data sets—all point clearly toward less than 50% of patients getting escalated therapy. Some of them were as low as 13%. Part of it is timing. The VA data sets ended in 2017 or 2018. It does look like there’s an improvement in terms of the percentage who are getting ADT plus. We can look at the 2019 data, but there are still less than 50%. It’s clear in my mind that it’s not even close to 50% who aren’t eligible for these drugs.

One of the data sets that Stephen Freedland presented showed not only that but even, unfortunately, increased disparities by race and ethnicity in terms of who’s getting them and who’s not in the world setting within an insured population. Luckily, 2 of these drugs are generic. Generic abiraterone in terms of lack of assistance co-pay may or may not be cheaper out of pocket, but docetaxel certainly is. It’s chemotherapy, so not everyone wants it or is appropriate for it. But at least that’s a very cost-effective drug. They’re actually all cost effective, but on a practical basis, it’s about how much the individual patients are paying out of pocket.

Transcript Edited for Clarity