John L. Marshall, MD: In your ReDOS study … it was a clever study that gave us the information that we were needing about how to dose this medicine REGO [regorafenib]. And not everybody knows about it because I think we’re still seeing people using full doses and the like. So quick, your study … I know it, but you did it.
Tanios S. Bekaii-Saab, MD: So ReDOS was a study trying to help us understand how to dose these. I mean these TKIs [tyrosine kinase inhibitors] are so challenging, across the board. It’s not just regorafenib.
John L. Marshall, MD: Well in REGO, too, I always have to remember that they did a basic one phase I study and then went to phase III.
Tanios S. Bekaii-Saab, MD: Exactly.
John L. Marshall, MD: So there was no real dose finding.
Tanios S. Bekaii-Saab, MD: And oftentimes that’s a challenge. That’s a challenge across oncology, how to dose right. But in this, in the first 2 weeks you start seeing these tough toxicities and patients drop off. But there was still the survival advantage despite that, which tells you that this is an active drug that we’re not dosing right. So we go back to the drawing table and we think about, so what is the strategy? There are different ways to think about strategies. One is, oh, you know what? Most patients get a 120 [mg/daily], so let’s do 120. But that doesn’t make sense because some still go to 80 and others, 20%-plus, go to 160.
And so we thought about dose escalation strategy. The goal is 160, and we start with 80. We add 40 every week to try to reach 160, as tolerated. And then the control arm was 160.
John L. Marshall, MD: Well the goal is really optimizing the dose, right?
Tanios S. Bekaii-Saab, MD: Yes.
John L. Marshall, MD: Not to get to 160.
Tanios S. Bekaii-Saab, MD: No.
John L. Marshall, MD: But just....
Tanios S. Bekaii-Saab, MD: Optimizing the dose. So that means a lot of patients may never make it to 160, and that’s OK. I mean if that’s the dose, because we know that when you start with 160, you deescalate for most patients. In this case we’re escalating rather than deescalating.
John L. Marshall, MD: And I’m seeing a couple of things. I’m seeing some folks who are still just doing the 160 and backing down and getting into the trouble we talked about. I’ve got others who start at 80 and never change. And then I’ve got those who started at 120s and never change, and you see them intermittently. But I actually say I’ve embraced the ReDOS strategy, and I see them often, make them get some LFTs [liver function tests] regularly. We’re in fact working on an app, which we hope will be pretty cool, that when a patient goes on they’re to report their [adverse] effects, and so instead of having to come and park their car, they could remotely tell you how they’re doing.
Tanios S. Bekaii-Saab, MD: That’s smart.
John L. Marshall, MD: And so we’re hoping that something like that will improve the optimization strategy. But what I found was really cool about your study was that there was an improved outcome. Now it’s a smaller study and we have to be careful here, but it was not worse—more people had longer therapy. And it, to me, re-reinforces this idea that don’t leave this drug on the table. If you’re going to have 20%, 25% of patients having a 6-months plus stable disease, that’s valuable. And I’ve gone to, as I present the drug to a patient, that’s what I say—about half of you will be stable, about a quarter of you are going to be stable by 6 months, and they get that.
Tricky though about prescribing. You know, there’s so much that we have to do that’s in tow with preauthorizations and the like. And we, our staff and team, have to do the [preauthorizations], and so we write prescriptions. And what I’m looking forward to is a label change that will enable us to modify the dose on the fly instead of either starting at 2 a day and having to reauthorize or; what do you guys do? Are you writing for the full dose, or?
Tanios S. Bekaii-Saab, MD: For now, yes.
John L. Marshall, MD: That’s really what you’ve got to do.
Tanios S. Bekaii-Saab, MD: That’s what we’re all doing, and then hopefully we’ll get that label changed at some point. We’re working on publishing the paper and hopefully once it gets published the company can go back to the agency and see if they … they can talk about it, they just can’t put it in the label right now.
Transcript Edited for Clarity