Unmet Needs in CINV

Transcript:

Lee S. Schwartzberg, MD: We’ve made great progress. We’ve talked about the new NK1s (neurokinin 1s); our 5-HT3s (5-hydroxytryptamine3s), which are very mature; and the use of corticosteroids and different ways of treating. So where are the remaining needs in CINV, and what are the unmet needs? Eric, what are your thoughts?

Eric Roeland, MD: We’ve done a good job of having guidelines classify chemotherapy broadly, but I think we need to incorporate those with patient risk factors and study this in a prospective way. So that’s 1 very important concern. The other is multiday chemotherapy. Currently, we take the worst offender and say that we’re going to classify their antiemetics based on that. But is that really the best option? If you’re getting a low or even moderate emetogenic chemotherapy [MEC] over multiple days, is that really high? This could then lead, of course, to the hematologic malignancy population, who really has been under-studied. It’s kind of the Wild, Wild West in terms of what people are doing with antiemetics in a very complicated and sick patient population.

Lee S. Schwartzberg, MD: What’s your experience? You mentioned BEP (bleomycin, etoposide, and platinum), Dawn, and that’s a regimen that’s tried-and-true for testicular cancer as multiple-day chemotherapy. Perhaps we don’t use quite as much of it, in general, as we did before, but there still are very specific reasons, and clearly, the hematologic malignancies, I would agree with Eric, are of concern. What are your thoughts? How do you approach multiday chemotherapy?

Dawn Dolan, PharmD, BCOP: We try to be as aggressive as possible in those particular patients. Like you had said before, these are curable patients. We do not need them falling off the wagon or coming back to us saying they don’t want therapy. We need to get them through, and we need to be aggressive, up front. In my personal opinion, I feel like we’re still underutilizing the NK1 receptor antagonists. We have all these great data, and we have all these drugs, but we still are seeing that 30% of the patients have nausea. One in 3 patients is still not being controlled. So we still have a ways to go.

Lee S. Schwartzberg, MD: Do you give the NK1 on day 1 and repeat it? And how do you approach palonosetron for the same point of view with a long-acting 5-HT3?

Dawn Dolan, PharmD, BCOP: Right now, we’re still doing only the NK1 on day 1. With palonosetron, if it’s a multiday regimen, we give it on days 1, 3, and 5 or every other day depending on the duration of the regimen.

Lee S. Schwartzberg, MD: Other thoughts?

Beth Eaby-Sandy, CRNP, OCN: I think one thing to touch on as an unmet need, and we see this a lot in the lung cancer population, especially with the ALK inhibitors, is that there’s a lot of nausea. And these are oral drugs that are dosed every day, sometimes twice a day. In my population of patients in lung cancer, especially with the ALK inhibitors, I struggle with how to manage nausea on an oral-targeted agent that’s taken every day, indefinitely, until disease progression. It’s sometimes, as I said, dosed twice a day. How do we manage that? Do they take a daily 5-HT3 orally? What would be the role of dexamethasone or an NK1? Because that’s for short term. I certainly don’t want somebody on dexamethasone every day. And then we think about the other breakthrough medications such as prochlorperazine or lorazepam, but they have toxicities as well. In my practice, that’s something that we’re struggling with—some of the oral targeted therapies and how to manage the nausea.

Howard Levine, PharmD: We built antiemetics in to some of our oral regimens. So we’ll give them, to start, ODTs (orally disintegrating tablets), for example. And if they come back and they say, “I’m continuously nauseated,” or they’re coming back or calling us saying, “We need more,” we have to reassess. We don’t know where we’re going with it, though. We really don’t know how to change them over to continuous therapy or not. Obviously, it’s not everybody, but for those patients who are resistant, who continually break through even though we’re not constantly treating them, we have to come up with a good way to treat them. We just don’t know what that is quite yet.

Lee S. Schwartzberg, MD: I think this is an area that’s very fertile ground for research. There’s really very little research on this, and I totally agree with you—the ALK inhibitors can be very significant. And you wonder about adherence with drugs. We do know that cancer patients do take their drugs more than others. But if you have chronic nausea, I suspect that there are patients who are saying, “I’m going to take a couple of days’ break and feel better.”

Beth Eaby-Sandy, CRNP, OCN: And many of which are recommended to take on an empty stomach.

Lee S. Schwartzberg, MD: Right, which makes it even more difficult. I’d like to see some trials with, perhaps, these long-acting NK1s. Maybe that would make a difference. As far as I’m aware, there have been no trials reported with that or even long-acting 5-HT3s. What about, even in our best efforts, situations where we have breakthrough nausea or even worse, refractory—where we’ve given therapies. What are your approaches now to breakthrough CINV?

Howard Levine, PharmD: Well, obviously, we look at what we’re doing to begin with. Our experience with breakthrough has not been terrible. We pretty much try to handle it, especially after the first cycle with the MEC patients who don’t do well. When we put them on combination regimens, they usually do pretty well, so we’re talking about a small percentage who are breaking through, overall, to a significant extent. If somebody once reports, “I was nauseated times 1,” we’re not really looking forward to making any changes, because it’s not affecting life dramatically.

That being said, we’re looking at what we’re going to supplement people with. We’re giving them long-acting everything, so where’s the supplement? If we’re giving them long-acting 5-HT3, do we give an additional 5-HT3? I’m not sure what the benefit is. There is no additional NK1. The question is, as Eric brought up, Is olanzapine something that we should be looking at, at that point? It might be a way to go, just for a different approach—a different mechanism, if you will—to see what’s happening. We know there are multiple receptors involved, and we’ve picked out the 2 most prominent to treat with our drugs, but it doesn’t mean dopamine isn’t the issue. It doesn’t mean other neurotransmitters are the issue in any particular patient. It’s kind of like the shotgun. At that point, let’s see what we have. And maybe olanzapine is the way to start.

Eric Roeland, MD: And that parallels your goals of keeping costs down. We’re talking about pennies, here, compared with some of these other drugs.

Dawn Dolan, PharmD, BCOP: You’ve got to look at other reasons for nausea and vomiting. In those ovarian patients with a lot of ascites or those head and neck cancer patients with a lot of secretions, can you get by with, potentially, adding an antihistamine or a scopolamine patch that might substantially decrease the additional nausea or dyspepsia? So thinking about those other little things that might be contributing to nausea on top of the chemotherapy regimen is important.

Beth Eaby-Sandy, CRNP, OCN: And I think remembering metoclopramide, as well, as a drug. If patients say to me, “I’m vomiting after eating a meal,” or, “I just feel full and then I’m nauseated,” something to increase gastrointestinal motility, such as metoclopramide, can have some play in that area as well.

Howard Levine, PharmD: You get delayed gastric emptying in a lot of these patients, too, secondary to the treatments. And metoclopramide reverses. That’s not a bad place to begin to think.

Lee S. Schwartzberg, MD: Also, GERD is another, and patients can experience that as nausea. As we talked about, nausea is multifactorial. It’s subjective, and there are many different ways you can get to that sensation of nausea, whether it’s anorexia or decreased gastric motility or the actual toxic effect of chemotherapy. So I think what I’m hearing is: careful patient history, particularly for breakthrough or refractory CINV, and then individualizing and personalizing dosing for that going forward, once you’ve established that you’re giving the most effective regimen. What do you think the future holds for CINV? Eric, what do you see going forward?

Eric Roeland, MD: I think it will always be an issue, even with our targeted agents. And I think that’s just because of these individualized risk factors that we’re still trying to tease out. We need to prioritize it and educate on all things we discussed and then deal with this in the real world. Currently, many of our decisions are being based on drug cost. So putting that all together is really where we need to go.

Lee S. Schwartzberg, MD: Other thoughts about future needs and unmet needs?

Howard Levine, PharmD: I think part of it right now, which we mentioned a couple of times, is education. The unmet need is, in my eyes, drugs are available to treat many more patients who are being treated. And unless you understand their role in therapy and apply it, it’s just not going to work. Obviously, the drug is great. If the patient doesn’t take it, it doesn’t do a thing for them. So getting to the grassroots level, the treatment level, and saying “Here’s what we have. Here’s what needs to be done for best practice.” And then, “What’s the best way to do it in your practice? What’s the best way to integrate this into your practice?” Because, obviously, based on surveys you mentioned, it’s not being used. Effective therapy is just not being used in the vast majority of patients.

Lee S. Schwartzberg, MD: To emphasize this point—education. Education of practitioners, education of the multidisciplinary team, and education, importantly, of patients to report back to us because this is a symptom that we can manage and hopefully prevent in the majority of patients. And even if we don’t prevent it, we have other ways of working on this.

Howard Levine, PharmD: Absolutely.

Dawn Dolan, PharmD, BCOP: Let’s take education a step further. Educate payers. We shouldn’t be running into situations where we have to beg to give the patient the correct regimen.

Lee S. Schwartzberg, MD: And we can, perhaps, educate them that the downstream costs, as we’ve mentioned, are something they need to focus on. It’s not just about the cost of the regimen. It’s understanding what the consequences are and that they’ll probably save money in the long run if we give the best therapy up front.

This has been an extremely informative discussion, and before we end it, I’d like to get closing thoughts from each of our panelists. I want to thank them for just an exceptional discussion. Dr Roeland, what are your closing thoughts?

Eric Roeland, MD: My closing thoughts are we should always stop and think. That’s true of many parts of our lives, but in this setting, improving our ability to control nausea and vomiting improves compliance and maximizes our ability to be aggressive.

Lee S. Schwartzberg, MD: Dr Dolan?

Dawn Dolan, PharmD, BCOP: I think we need to be more cognizant of guidelines and not become complacent. There are still unmet needs out there. We still have patients with issues, and we just need to take our research a step further.

Lee S. Schwartzberg, MD: Thank you. Ms. Eaby-Sandy?

Beth Eaby-Sandy, CRNP, OCN: Know your patient, do a thorough review and patient history, and understand what is causing their nausea, besides the drug that you’re giving them. And then tailor your approach to managing it based on the patient.

Lee S. Schwartzberg, MD: Thank you. Dr. Levine?

Howard Levine, PharmD: I have to agree. It’s about individualizing treatments—per patient, per treatment, per their history. Put it all together and take the time to make that decision. Most importantly, up front day 1 is when you have the most impact. Do it up front and you will save patient dissatisfaction with treatment. You will have better therapies in the long run, and everybody will benefit from it.

Lee S. Schwartzberg, MD: In 2017, one of the buzzwords is personalized medicine, and what we’re saying is to personalize medicine as it relates to the prophylaxis of CINV. This is critical as well.

Howard Levine, PharmD: Absolutely.

Lee S. Schwartzberg, MD: Thank you all for your contributions to this discussion. On behalf of our excellent panel, we thank you for joining us, and we hope you found this Peer Exchange^® discussion to be useful and informative.

Transcript Edited for Clarity