Management of Chemotherapy-Induced Nausea & Vomiting - Episode 8
Transcript:Lee S. Schwartzberg, MD: In the last couple of years, things have changed a lot because we have a couple of new agents in the NK1 field, which is nice. It was the early 2000’s when aprepitant came out, and around 2008 when the fosaprepitant studies were completed and showing non-inferiority. So, now we have new drugs. Let’s talk about those a little bit.
Eric Roeland, MD: One new kid on the block is netupitant, which is only available in combination with palonosetron. The name of NEPA emerged, which is netupitant plus palonosetron, or the brand name is Akynzeo. That has several advantages. One is the netupitant has a very long half-life, and two is you’re combining it with palonosetron, which many of us prefer. With oral palonosetron, sometimes people in the United States are wondering about that. But, it turns out the rest of the world, including all of Europe, uses oral palonosetron and the studies show that they’re equivalent. Right, Jim?
James Natale, PharmD, BCOP: That is absolutely right. Although, that was a question our doctors were asking. And everybody was talking about it: oral palonosetron.
Lee S. Schwartzberg, MD: But, every 5-HT3 receptor antagonist has been tested in the IV versus oral form, and they’re all equal—all the first generations, as well as palonosetron. We just don’t have it available in the United States as a single agent.
Eric Roeland, MD: Yes. Netupitant is only in combination with palonosetron as a pill, which, depending on the practice, can be a major advantage or disadvantage in terms of funding and payment. What I do like about it is its one simple pill to take. And, basically, it encapsulates the guidelines in that you’re getting the 5-HT3 with the NK1. So, I think it’s a promising tool. You can’t get netupitant by itself; it’s always in combination.
Lee S. Schwartzberg, MD: And you can have an oral regimen here. You can have the one pill of Akynzeo plus dexamethasone orally. So, for the patients who would prefer that, or if the flow in the practice would allow that, that’s an option, right?
Eric Roeland, MD: Yes, and it’s been studied in highly emetogenic chemotherapy not only in the first cycle, but in multiple cycles. It’s been studied in AC (anthracycline/cyclophosphamide), which is a tough patient population, and it’s been studied in MEC. So, there are some good data on it.
Lee S. Schwartzberg, MD: What other drugs have come out? Jim?
James Natale, PharmD, BCOP: Well, I guess the other NK1 agent that’s now available is Varubi, or rolapitant, which just has been approved not so long ago. Again, it’s an oral agent. It’s going to be recommended to be used in combination with 5-HT3 in HEC, plus steroids. That, as I said, recently has been approved. It also has a much longer half-life. And that’s probably been one of the bigger changes, at least in the landscape of these agents. Inherently, the molecule itself has a much longer half-life, when you compare it to, say, the first generation 5-HT3 with up to a 9-hour half-life, depending upon the product. So, these inherently have longer half-lives. And, then, probably even more importantly, there are data now that show that they stay on the receptor for that whole period of both acute and delayed, which I think has been an advantage for the newer agents.
Eric Roeland, MD: With these new agents, and they’re a class, they’re all NK1 receptor antagonists, I try to think of what is the advantage of each of them and each niche. And the one when I think with rolapitant, or Varubi, is the 384. It has decreased 384 interactions. And so, in those patients that are on a bunch of other medications, and your pharmacist is calling you about all the drug-drug interactions, this is something for us to think about.
Lee S. Schwartzberg, MD: We should mention actually, because we didn’t talk about that for aprepitant, the interaction and dose adjustments, particularly dexamethasone. Someone wants to talk about that.
Charles L. Loprinzi, MD: They’re arguing about the dose for dexamethasone, but oftentimes it’s 20 mg that we use for highly emetogenic chemotherapy. But, because of this interaction, 12 mg of dexamethasone, when you give it with aprepitant, is equal to 20 mg you would give without that. So, those studies adjust for that aspect of things.
The thing is, just to carry on with what you’re saying there, we don’t really have any comparative trial from the four different NK1 receptor antagonists. We’re not likely to get that sort of a trial there and they seem pretty similar. Fair?
Eric Roeland, MD: I think there’s the niche in your payment model and where you’re at. And so, this is allowing us to get a good class of medications into patients in a variety of ways. And if you’re looking at someone—we’ll discuss, I’m sure, multi-day chemotherapies on immunosuppressives—say, in the BMT setting or something, I feel like rolapitant has a bigger role. If you have a patient that’s really far from home or from the cancer center, maybe the oral drug is a nice patient-centered alternative. So, I just try to think about that. But, of course, institutional guidelines and payments often limit which options we can choose.
Lee S. Schwartzberg, MD: What kind of clinical experience have you see with this? Jim?
James Natale, PharmD, BCOP: I can only speak on the Akynzeo side. We certainly have looked at using it in some unique patient populations, one of them being our autologous transplant patients that have multiple myeloma. They’re receiving high-dose melphalan on the inpatient side of things. We’ve used Akynzeo actually very effectively for 1 day prior to their prep regimen to get their transplant. The other place that we have some clinical experience with Akynzeo is a 5A platinum, where patients on that fit the platinum therapy that will be given Akynzeo, particularly those patients that do live far away. As I mentioned earlier, we are a referral center, so we get patients from all over western Pennsylvania, eastern Ohio, and northern West Virginia areas. So, we’ll give them a three-drug regimen for the first 4 days with some of the shorter acting agents. And, then, on day 5, use Akynzeo so when they leave the clinic, they’ll be covered in that delayed phase and utilize the pharmacokinetics with the new drugs.
Lee S. Schwartzberg, MD: I had some experience in the clinical trials with both the NEPA and rolapitant, and I was impressed in the clinical trials on the efficacy of both. And recently, we have started to integrate the use of the oral agents into our clinic. You have to work out your operational flow there, but we’ve seen when we use these drugs that they’re both long acting. I think that’s an important aspect of them, as you said, so you can give them once, and then don’t have to worry about that. They’ve been effective. And, I think it just takes some preparation in terms of how you adjust the flow in the clinic of giving your supportive care of medications, and also making sure that the benefits are structured right for the patients, however they’re acquiring the drug, as well. So, if you have, as we do, a dispensing pharmacy, that may be one opportunity to use these drugs, and to really fit the flow in nicely.
James Natale, PharmD, BCOP: I totally agree with you, Lee. The other thing, a little work may need to be done on the front end. Some of the local insurers may try to tier these newer oral agents. So, there may be some work done or that needs to be done on the front end to make sure that there’s coverage, and that they’re really put on the same tier as some of the older agents. But, once that happens, we’ve had really good success with Akynzeo, at least in those specific populations that we started using it on. And we’ve also seen it used in some refractory patients, that they’ve gotten5-HT3, NK1, and steroids. We switched over to Akynzeo, and that seemed to be effective in those refractory patients; not all of them, but a good majority of them.
Lee S. Schwartzberg, MD: Yes. The other opportunity for Varubi and Akynzeo is to reduce chair time, potentially when you have a busy practice. In my own practice, everybody seems to want to get treated between 10AM and 2PM, so it looks like a train station in there. So, there are opportunities for the practice flow as well.
Transcript Edited for Clarity