Management of Chemotherapy-Induced Nausea and Vomiting (CINV) - Episode 10

5-HT3/NK1 Receptor Antagonist Combinations for CINV


Lee S. Schwartzberg, MD: Howard, the other drug that we have that is perhaps the most convenient is NEPA, which is a combination of netupitant and palonosetron in 1 capsule. And so that can be an oral regimen with 1 capsule as well as with dexamethasone, orally. Are you using that, and how is that working for you?

Howard Levine, PharmD: Well, the answer is yes, we do use it. We have about a year-and-a-half experience with it now, with great success. It works. Our practice does have dispensing in the practice, which makes it a little bit easier from a logistic situation. The dispensing pharmacy is connected to the treatment area. So when the drug comes in and the order comes in, we have it ready for the patient. The pharmacist goes out, watches the patient take the medication, and then the line is started. And by the time everything gets going, it’s an hour-plus before treatment, which is good. We see the patient take it, so there’s no issue. Prior to availability of the combination, we were using oral aprepitant.

Lee S. Schwartzberg, MD: Oh, you were?

Howard Levine, PharmD: Magically, they would take their drugs. We had very, very little patient failure, on that end. They would take the medication and do well. When we looked at the new NK1 antagonists—again, we were in practice for 12 years, at least, since I’d been there—we looked at efficacy among the new NK1 drugs, and they were all pretty much the same. I didn’t see much of a difference. You could tease out differences depending on how you do any study. But the reality is they all worked. So efficacy in our eyes was never an issue among the choices. With safety, also, and similar safety profiles, there are little differences here and there, but they are all pretty much the same. For us, it was making the decision on whether to go to the more convenient step, which was using the oral regimen across the board. And the answer was, “Yes, we’re going to do that.”

And, as was mentioned, this reduced chair time because we didn’t have to worry about getting the Aloxi ready for our patient, which was nice. We never gave IV NK1s anyway, so that was not part of our package. We just sort of swapped it out. And it was easy with the EMR to switch one in and one out. It’s our standard. We also have it as the backup after HEC (highly emetogenic chemotherapy) regimens, where it’s built in. It’s the PRN choice. So if a patient is somebody whom we expect to do poorly from risk factors, or they’ve done poorly in past, we automatically have it built in, and everything is ready to go.

Some of the issues are in prior authorizations with PO drugs, which, in some cases, make things more difficult. They don’t want to hear it. It’s insurance companies, but it’s going to cost more on the medical side, for example, to do this. But that’s the medical people paying. We’re the pharmacy benefit people. We don’t care about what they pay, and for us, it’s the overall cost. You have to sort of filter through all that stuff and make some sense of it. But we try to get it for our patients. We’ve been pretty successful, I’m going to say, 75% of the time, in getting this approved for our patients. We do use some rolapitant. Strangely, insurance companies will approve one versus the other.

Lee S. Schwartzberg, MD: They will approve palonosetron but not NEPA. Or they will approve ondansetron.

Howard Levine, PharmD: They’ll approve Varuby, and they won’t approve Akynzeo. They’ll approve Emend but won’t approve either of the other 2, even though Emend costs more than the other 2. I don’t understand that.

Beth Eaby-Sandy, CRNP, OCN: I ran into a similar situation yesterday. For my 46-year-old female patient, I prescribed the netupitant/palonosetron pill. I got a call from my pharmacy, which is right underneath us, so it’s very close, and they said her plan requires a stepwise approach. So I called the plan, and they said they wanted her to fail aprepitant or fosaprepitant and ondansetron before approving my suggestion. And I said, “Can we go to the NCCN guideline website together and see if either option is approved?” It is not a stepwise approach, and they did not budge on it. They said, “This is the way that we’re doing it. This is a managed care organization. This is our stepwise approach, so this person must fail ondansetron and either aprepitant or fosaprepitant before we would approve either rolapitant or the netupitant/palonosetron option.”

Lee S. Schwartzberg, MD: So to be clear, that doesn’t make medical sense, and it’s really just an arbitrary decision.

Beth Eaby-Sandy, CRNP, OCN: We went together to the NCCN guideline website and pulled it up, and I said, “These are options. There is not a 1-fail, this is better than, at all. These are options that you have that work equally.”

Howard Levine, PharmD: The actuary made that decision, I guess, and not the clinician.

Lee S. Schwartzberg, MD: Right.

Eric Roeland, MD: It’s also very much a cultural phenomenon because when you talk to Europeans or Australians, everything is oral. And when we talk about these reimbursement issues, they just laugh at us. It’s interesting that we have been so IV focused, based on reimbursement, when we know the efficacy is equal.

Lee S. Schwartzberg, MD: Right. I think the point is that they are equal and it’s changing, it sounds like from this discussion, which is very interesting. And we’re moving for a couple of dynamics, perhaps from IV to oral, but there are going to be situations where we need both. One thing we haven’t talked about, specifically, is toxicity—incremental toxicity of NK1. What are your thoughts on that, Dawn? And when you add it to your 5-HT3 and dexamethasone, what more do you get in terms of toxicity?

Dawn Dolan, PharmD, BCOP: What we’re finding is that it really doesn’t add a whole lot of additional toxicity. We’re seeing a few little things like fatigue and hiccups, but I often attribute that to the dexamethasone. We are aware that all the NK1s have drug interactions except rolapitant, so we do have to make some dexamethasone adjustments. And so there might be some additional play there with the augmentation of the dexamethasone and, maybe, adding to some of that hiccup issue. But it’s also a funny thing because hiccups can be related to nausea and vomiting. So it all comes full circle. In general, we’re seeing that the NK1s really don’t add an incremental increase in toxicity at all.

Lee S. Schwartzberg, MD: That was our experience in the clinical trials, and that’s my experience, as well, in the clinic. Does everyone else agree with that?

Howard Levine, PharmD: I have the same experience.

Lee S. Schwartzberg, MD: Very little incremental toxicity, which is another reason to be more proactive when using it, as opposed to less if we take cost into consideration.

Transcript Edited for Clarity