Updates on Anti-Emetics Guidelines and Checkpoint Inhibitor Implications

An interview with Dr. Paul J. Hesketh from Lahey Hospital and Medical Center in Burlington, MA on "Antiemetics: ASCO Guideline Update." This update addresses antiemetic prophylaxis in patients treated with checkpoint inhibitors and incorporates new data since the last guideline publication. Read the full guideline at www.asco.org/supportive-care-guidelines

TRANSCRIPT

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello, and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org. My name is Brittany Harvey. And today, I'm interviewing Dr. Paul Hesketh from Lahey Hospital and Medical Center in Burlington, Massachusetts, co-chair of antiemetics, ASCO Guideline update. Thanks for joining me, Dr. Kesketh.

Hello, Brittany. I'm very happy to have the opportunity to join in today's podcast.

First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Hesketh, do you have any relevant disclosures directly related to this guideline topic?

No, I do not have any relevant disclosures.

So, Dr. Hesketh, what prompted an update to this an antiemetics guideline, which was last published in 2017?

Well, as you know, Brittany, each guideline panel is instructed by ASCO to regularly review the evolving literature and other information, looking for any significant developments that are relevant to that specific guideline. And since our last update in 2017, there has been a tremendous expansion in the use of checkpoint inhibitors for a variety of different neoplastic diseases. Although they're often used alone, increasingly, the checkpoint inhibitors were being added to a variety of chemotherapy regimens. And as this was occurring, concerns were being expressed by some oncologists that corticosteroids, a critical component of many antiemetic regimens, might be contraindicated when checkpoint inhibitors were being added to chemotherapy regimens given the potential immunosuppressive possibility for corticosteroids. So the panel felt that an update was indicated to try to address this issue as well as providing information on new antiemetics, antiemetic regimens, and to try to categorize the medic potential of the many new anticancer agents that have been approved since our last update.

Great. So you touched on a couple things there. So first, how does the guideline address antiemetic prophylaxis in patients treated with checkpoint inhibitors?

Well, the search that we conducted for this guideline found 10 relevant publication on checkpoint inhibitors. The search reaffirmed the panel's conclusion that all currently available checkpoint inhibitors really have minimal emetic potential when used as monotherapy. And really, no prophylactic antiemetics are required when an individual checkpoint inhibitor is used.

When used in combination with chemotherapy, two phase III trials were particularly instructive in helping to formulate our guidelines. Both trials were conducted in adult patients with non-small cell lung cancers treated with a platinum based doublet with or without the Program Death 1, PD-1 inhibitor pembrolizumab. And they recommended in both those studies that all patients receive dexamethasone as a component of the prophylactic antiemetic regiment. And of note, in both studies, superior efficacy outcomes were noted in the PD-1 inhibitor containing harms. Therefore, the panel feels that there is really no clinical evidence at present to warrant emission of dexamethasone from guideline compliant prophylactic antiemetic regiments when checkpoint inhibitors are administered to adults in combination with chemotherapy.

And then you touched on also antiemetic regimens that were updated. Given the new information about olanzapine, what recommendations were updated?

Well, olanzapine is a very interesting drug. It's a second generation antipsychotic which, very interestingly, has significant antiemetic properties. And the updated guidelines reaffirms the role of olanzapine as part of antiemetic prophylaxis when one administers highly emetogenic chemotherapy regimens. And it also can be very useful as a rescue agent in patients developing emesis despite appropriate prophylaxis.

So the new studies that were published since our last update have demonstrated the value of adding olanzapine to a 5-HT3 receptor antagonist, dexamethasone, and an NK-1 receptor antagonist used in the setting of high dose chemotherapy when used with hematopoietic stem cell transplantation. In addition, the prior recommendations only specified a 10 milligram dose of olanzapine as the only option. We now have data from an updated study that a 5 milligram dose is an acceptable alternative to the 10 milligram dose when used in the setting of highly emetogenic chemotherapy.

Great. Thanks for reviewing that information. So what in your view is the importance of this guideline for clinical practice?

Well, we have made really enormous progress in developing effective means to prevent treatment induced nausea and vomiting in patients with cancer. Each update of the guidelines, the current version included, have provided additional valuable insight for clinicians to help further limit the frequency of this potential side effect of cancer treatment. The most important aspect of the current update will be providing reassurance to clinicians that effective antiemetic prophylactic regimens do not need to be compromised when the new checkpoint inhibitors are administered in combination with emetogenic chemotherapy regiments. In addition to the new information on olanzapine, the update also notes the addition of useful new IV formulations of aprepitant and the combination agent netupitant and palonosetron. In addition, we have information on the use of fosaprepitant and as an option when an NK-1 receptor antagonist is indicated in the pediatric setting.

And then finally, how do you view that these recommendations will impact patients?

Well, we know from many patient surveys that treatment induced nausea and vomiting are among the most dreaded potential side effects that patients worry about when they think about starting cancer treatment, especially if they're going to be receiving chemotherapy. So fortunately, we now have extremely effective and well tolerated antiemetic regiments for all treatment settings. However, patients will only benefit if these evidence-based regimens are utilized in a manner consistent with the ASCO guidelines. So we hope that this guideline update will provide useful information for ecology providers to really optimize the prevention of nausea and vomiting in patients receiving various emetogenic type of treatment regimens.

Well, thank you so much for your work on this ASCO guideline update on antiemetics and for taking the time to speak with me today, Dr. Hesketh.

Thanks very much, Brittany. Happy to do so.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app available in iTunes or the Google Play store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.