Management of Chemotherapy-Induced Nausea and Vomiting (CINV) - Episode 9

Role of NK1 Receptor Antagonists in Treating CINV


Lee S. Schwartzberg, MD: We talked about 5-HT3 receptors and acute chemotherapy-induced nausea and vomiting. They’re very effective in the acute setting but not as effective in delayed CINV. We’ve learned, from pathophysiology over time, that the NK1 receptors are more important in that area. Beth, can you talk a little bit about our approaches to NK1 antagonists and what we have available?

Beth Eaby-Sandy, CRNP, OCN: I think adding these to 5-HT3s has dramatically improved our control in the delayed setting. Not that we’re doing 100% better, but I think with the addition of these drugs—the way that we understand substance P binding with NK1, which may be giving a longer binding—we’re controlling the delayed setting of nausea/vomiting better with these drugs.

There are several drugs now in this category. Oral aprepitant was the first one that was approved, and then fosaprepitant, which is the intravenous form of aprepitant, was approved later on. Now we have rolapitant, as well, which has a much longer half-life. That can be dosed on day 1 and can have coverage for up to 7 days or even longer, technically. So I think the addition of these drugs has really been a benefit to us. There’s also netupitant, which is part of an NK1 that’s part of a combination pill. We’ll talk about that as well. Therefore, there are technically 4 drugs now in this category.

Lee S. Schwartzberg, MD: How has that changed things? Where are you using NK1 receptor antagonists?

Beth Eaby-Sandy, CRNP, OCN: That is built in, absolutely, to our highly emetogenic regimens, and then it’s an option for our moderately emetogenic regimens. Now, if you look at the NCCN guidelines, it’s absolutely approved for both moderately and highly emetogenic patients—really, all these drugs in this category are. Some practices will say, “I’m going to make a call on it, on the moderately emetogenic regimen, based on patient risk factors.” Some practices will automatically put it into every single regimen. It really depends on your patient population. At our institution, we’re very much tasked right now with cost and savings of cost.

Dawn Dolan, PharmD, BCOP: The NK1s, I think, are still underutilized—especially in the MEC (moderately emetogenic chemotherapy) setting. And what I found really refreshing is that the guidelines now lay it out there that it’s definitely an option. I’m hoping that that makes the payers follow suit so that we are able to, maybe, give these drugs. We’re always told to use the best drugs that we have, up front, to prevent, prevent, prevent. But we’re still not really able to facilitate doing that in all of our patient population.

Lee S. Schwartzberg, MD: You’re harkening back to the beginning of our discussion today. We have guidelines. They’re very specific and clear about who should get triplet therapy—HEC (highly emetogenic chemotherapy) patients now; carboplatin patients have moved up there; AC (cyclophosphamide/doxorubicin)-regimen patients; platinum, at the least. And we still have this range of MEC where it’s totally acceptable to give it, and we’re all using patient risk factors. But it’s so fascinating that despite the fact that we have guidelines, if you look at usage in surveys, there’s still a significant percentage of patients, even with HEC, who aren’t getting an NK1 antagonist. Do people have thoughts on why that is? Is that related to cost, not thinking about it? What are your feelings?

Beth Eaby-Sandy, CRNP, OCN: They must not have an EMR.

Dawn Dolan, PharmD, BCOP: That, and I don’t want to harp on the community ones, but they may not have the multidisciplinary approaches to the way they treat care, so they may not have those extra people. I know sometimes I’m considered a wife in their ear, saying, “Hey, don’t forget this, and don’t forget this.” But it’s that extra reinforcement in making sure that we’re following guideline-based therapy.

Howard Levine, PharmD: Yes. I’d be interested to see who is not using it. Is it segregated by small community practice versus institutional practice? My guess is, in some ways, it is. As you suggest, there’s not somebody there to say, “Build this into your standard treatments.” If it’s not built in, it becomes an afterthought. If you bring it up to that physician, of course they’ll add it. But why weren’t they using it up front? There’s probably something that was never put in place, and this has been years and years and years now. This is not new, but nobody really stepped up and said, “Put this in place to start, and your patients will do well.”

Lee S. Schwartzberg, MD: Let’s talk about the route of administration of the NK1s. We talked about the fact that the first drug approved was aprepitant, and the oral aprepitant had to be given in a loading dose and then 2 additional days, which was difficult. Then we had an IV form. Now we have the newer drugs—rolapitant, currently given orally, and an IV form is coming. So let’s talk about, first of all, efficacy. What’s your experience with efficacy in terms of oral rolapitant versus other agents—and particularly IV?

Beth Eaby-Sandy, CRNP, OCN: I have very limited use with oral rolapitant, but I’ve had some. I don’t think the efficacy is that big of a difference. I think they’re efficacious whether you give them as oral or IV therapy. The route of administration is the issue. An oral is a prescription that the patient has to get, and they have to grapple with a prior authorization or a co-pay. Now, that being said, with fosaprepitant, which is IV, lately we’ve had to prior-authorize that as well as part of our chemotherapy regimen. We actually have to prior-authorize fosaprepitant and palonosetron with several of our managed care patients.

Lee S. Schwartzberg, MD: Even on guideline?

Beth Eaby-Sandy, CRNP, OCN: Even on guideline. Absolutely, on guideline. So when we pre-certify our chemotherapy, we’re now being asked, “What is your antiemetic regimen?” Or we’re being told, “Make sure you add that if you’re planning to use palonosetron or fosaprepitant as part of their IV.” Now, if it’s oral, it’s going to come back to my office, but we have a chemotherapy precertification person who is doing that. They are asking us to make sure that if you’re going to include those 2 drugs that we prior-authorize them. This is required for some of the insurance companies but not all. The upside of the orals, for us, has been the fact that we don’t have to waste chair time for them to get an IV. And it’s not just chair time, but it’s pharmacy mixing time. It’s prior authorization time. The ability for them to take a pill while they’re waiting in my waiting room—and that they can go back and just get their chemotherapy and go home—has actually been something that’s been nice for us. It’s been a benefit. If you have a relationship with a pharmacy, especially an in-house pharmacy that can dispense, or if you are a dispensing pharmacy, I think there is an upside to the orals based on that. I think there are pros and cons of that route of administration.

From an efficacy standpoint, I can tell you the first time I gave an oral and then cisplatin, and there was nothing going through their IV, I was like, “Oh, please work.” And the patients would come back 3 weeks later and say, “Yes, it was great. I had no nausea.” And my thought would be, “OK, it works.” Obviously, there are clinical trial data to say that, but I’ve been so used to using IVs for my whole career. Even when oral aprepitant was approved, at least they still had the IV 5-HT3. Now if I’m using an all-oral regimen, initially I had to get used to it, especially with the cisplatin patients.

Lee S. Schwartzberg, MD: Yes. Old habits die hard.

Beth Eaby-Sandy, CRNP, OCN: Oh, yes.

Lee S. Schwartzberg, MD: You’re also giving a pill for advanced lung cancer in certain instances, and it works really well. So things are changing. I agree with you—you have that moment of, “Am I doing the right thing?”

Beth Eaby-Sandy, CRNP, OCN: Boy, did I have a moment.

Lee S. Schwartzberg, MD: In the rolapitant studies that we did, it worked wonderfully in AC patients and in platinum patients—in both HEC and what we called MEC then, which is now HEC. So we are very comfortable with that. There are changing reimbursement strategies. You bring up this whole issue: For some patients, from a reimbursement and from the practice burden on prior-authorizations standpoint, it might be better to do IV. And in some, it may, interestingly, be better to do orals.

Lee S. Schwartzberg, MD: We’ve talked a lot about the NK1s and the orals. How will we use IV rolapitant, which is imminent in being approved, and where do you see the value of that particular agent? It can be started at room temperature, which makes it easy for the pharmacist.

Howard Levine, PharmD: It’s interesting because we’re the outlier. We’ve always used oral therapy, and we admit we’re the outlier. That being the case, I look at it, again, as logistically, How does it fit into your practice? If oral treatments are difficult because you’re dependent on somebody outside to provide the medication, and if the patient didn’t bring it or take it before they came in, you might say, “IV is our choice because we see it administered and it’s there. We have confidence.” On the other hand, if you can reliably prescribe and get the patient the medications orally, it should work just as well. I’m assuming that the efficacies are going to be the same. So that being the case, it becomes a practice decision as to what fits, logistically, into what they do, in my eyes.

Lee S. Schwartzberg, MD: For practices that are designed to deliver the IV antiemetics, that’s how our practice has administered, over a long period of time, this will fit in beautifully. It will be substitution. We’ll have a new agent that has fewer interactions and also has a long half-life and long exposure so that you don’t have to give it again. It will fit in very nicely for us, and there may be fewer storage fees associated with it as well.

Dawn Dolan, PharmD, BCOP: I think it will be ideal for the multiday regimens, most of which just happen to have cisplatin in them. So across disease sites, I think that will be an ideal option for a day 1 management of a multiday regimen.

Eric Roeland, MD: I also think for the hematologic malignancies where we are worried about all the drug—drug interactions and mucositis, it has a really nice niche there.

Dawn Dolan, PharmD, BCOP: Yes. I agree with all of you. Howard, you said you’re the outlier. You’re living utopia. For those of us who are not able to facilitate oral treatments, this is going to be a nice addition.

Transcript Edited for Clarity