The ASCO guideline on the use of antiemetics has been updated to include new anticancer agents, antiemetics, and regimens.1 The guideline also addresses a growing concern among some oncologists that corticosteroids and their immunosuppressive abilities could potentially compromise the efficacy of therapeutic checkpoint inhibitors that are often combined with chemotherapy. The corticosteroid dexamethasone is used in multiple antiemetic guideline-endorsed regimens to prevent nausea and vomiting caused by chemotherapy.
Paul J. Hesketh, MD, FASCO
“We assessed new antiemetic agents and regimens, new uses for previously approved antiemetics, and categorized the emetic potential of the tremendous number of new anticancer agents approved since 2017,” said Guideline Co-Chair Paul J. Hesketh, MD, FASCO, of the Lahey Hospital & Medical Center, Burlington, Massachusetts.
Dexamethasone and Checkpoint Inhibitors
An expert panel assessed clinical evidence from randomized controlled trials and meta-analyses of randomized controlled trials published between 2016 and 2020. The updated guideline follows a significant expansion in the use of checkpoint inhibitors to treat a variety of cancers since the previous guideline was published in 2017.
“The addition of checkpoint inhibitors to chemotherapy regimens prompted a concern by some in the oncology community that dexamethasone might potentially compromise the efficacy of checkpoint inhibitors,” Dr. Hesketh said.
Two phase III trials involving adults with non–small cell lung cancer were particularly instructive in addressing this concern, Dr. Hesketh noted. The trials evaluated a platinum-based doublet with or without the PD-1 inhibitor pembrolizumab and recommended all patients receive dexamethasone as a component of the prophylactic antiemetic regimen. Superior efficacy outcomes were noted in the PD-1 inhibitor–containing arms of both studies.
The expert panel found no clinical evidence to warrant the omission of dexamethasone from the existing guideline on prophylactic antiemetic regimens when checkpoint inhibitors are administered to adults in combination with chemotherapy. The data suggested there was no compromise in the efficacy of checkpoint inhibitors with dexamethasone.
“There was no evidence whatsoever in the data that dexamethasone somehow negated the effects of checkpoint inhibitors,” said Guideline Co-Chair Mark G. Kris, MD, FASCO, of Memorial Sloan Kettering Cancer Center, New York. “The other key point is that when people take dexamethasone as an antiemetic, it’s for a few days each month; the studies that raised concerns involved patients who were taking it chronically.”
Mark G. Kris, MD, FASCO
The guideline recommended that, when checkpoint inhibitors were administered alone or in combination with another checkpoint inhibitor without the addition of chemotherapy, the routine use of a prophylactic antiemetic was not required.
Reducing Nausea and Vomiting
Dr. Kris said the recommendations on antiemetics are critically important because nausea and vomiting are often the most feared adverse effects by patients before chemotherapy begins. And they cause the most intolerable side effects for many patients.
“We would never want to give less than guideline-mandated treatments to our patients,” Dr. Kris said. “It is important for the entire oncology team to make it very clear at the start of cancer therapy that if the treatment has a risk of nausea and vomiting, the patient [must be] reassured the team will do the maximum [possible] to prevent these side effects,” he added.
New data prompted the recommendation of adding olanzapine in the hematopoietic stem cell transplant setting and provided the option of using a new 5-mg dose of olanzapine in adults receiving highly emetic chemotherapy. “The data show that olanzapine is a safe and effective antiemetic in high-risk emetic settings, as well as demonstrate value in lessening nausea and vomiting in patients when used as a breakthrough agent,” Dr. Hesketh commented.
Although the guideline recommendations pertain mainly to adults, particularly on the use of checkpoint inhibitors with antiemetics containing corticosteroids, they also address the needs of the pediatric patient population. The guideline update adds fosaprepitant as another option in this population to prevent nausea and vomiting when a neurokinin-1 receptor antagonist is indicated.
The expert panel did not find sufficient evidence to make a recommendation on the use of medical marijuana for the prevention of nausea and vomiting in patients receiving chemotherapy or radiation therapy. However, Dr. Kris said further studies should be conducted on the use of cannabinoids to address the needs of patients.
“We have cannabinoid receptors in our brains, and we need to know how to use them in a way that fulfills the needs of our patients. So, going forward, that is something we need to explore,” commented Dr. Kris.
DISCLOSURE: Dr. Hesketh has received institutional research funding from AstraZeneca and F. Hoffmann–La Roche AG. Dr. Kris has served as a consultant or advisor to AstraZeneca, Daiichi Sankyo, and Pfizer; has been reimbursed for travel, accommodations, or other expenses by AstraZeneca and Pfizer; and has held other relationships with Genentech/Roche and Memorial Sloan Kettering Cancer Center. For full disclosures of other panel members, visit ascopubs.org.
1. Hesketh PJ, Kris MG, Basch E, et al: Antiemetics: ASCO guideline update. J Clin Oncol. July 13, 2020 (early release online).
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, July 15, 2020. All rights reserved.