Pharmacists play an invaluable role on the oncology care team for the management of chemotherapy-induced nausea and vomiting (CINV). But although the pipeline for new cancer drugs expands, the number of novel antiemetics in the pipeline is drying up, underlining the importance of the pharmacist’s knowledge of the available antiemetics for patients undergoing chemotherapy, said Michael J. Berger, PharmD, BCOP, Clinical Specialty Pharmacist, The James Cancer Hospital at The Ohio State University Wexner Medical Center, Columbus, at the 2019 Hematology/Oncology Pharmacy Association (HOPA) annual meeting.
“Providers are going to look at you and expect you to know what to do,” said Dr Berger. It is therefore up to the pharmacist to guard against over- or underutilization of antiemetics, while also being knowledgeable of drug properties, drug interactions, clinical trial results, clinical practice guidelines, and cost, because these factors all play a role in antiemetic selection.
Dr Berger provided an in-depth overview of current guidelines, recently approved agents, and controversies surrounding the management of CINV, and highlighted key takeaways for practicing pharmacists.
Determining Emetogenic Risk
A risk assessment for CINV, with appropriate interventions, should be completed on each patient before the start of anticancer therapy and before any subsequent chemotherapy cycles. Prophylactic medications should be scheduled throughout the risk period: 4 days for a single-day highly emetogenic chemotherapy (HEC) regimen, and 3 days for moderately emetogenic chemotherapy (MEC) regimen. Pharmacists should also ensure they have a breakthrough medication from a different pharmacologic class, he advised.
“CINV is much easier to prevent than it is to treat,” he said. “It’s really key to counsel our patients to make sure they understand how important it is to be compliant with their scheduled medications, and to use breakthrough the moment they start to feel nauseous.”
Determining emetogenic risk is fairly straightforward when administering a single-agent MEC regimen, but when using more than 1 drug, the risk should be based on the drug in the regimen with the highest emetic risk. For example, cisplatin (high risk) plus etoposide (low risk) would be HEC, whereas oxaliplatin (moderate risk) plus fluorouracil (5FU; low risk) plus leucovorin (minimal risk) would be MEC. In the case of 2 moderately emetogenic drugs (ie, anthracycline plus cyclophosphamide), consider the regimen as HEC.
According to Dr Berger, nausea remains a more significant problem than vomiting. Many physicians and nurses think that CINV is fairly well-controlled, but patient perceptions are usually different. A 2015 HOPA survey revealed wide misconceptions about CINV held by patients. Many patients thought that nausea and vomiting meant their chemotherapy was working, or that CINV was simply to be expected. Survey respondents also often thought that as long as they were not vomiting, their CINV was controlled.
“So, we’ve got a little work to do there,” he noted.
Olanzapine has been shown to improve outcomes when added to a prophylactic 3-drug regimen—neurokinin-1 (NK1) receptor antagonist plus serotonin (5-HT3) receptor antagonist plus dexamethasone—and is now considered a standard of care option for cisplatin-based and other HEC regimens, according to the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) guidelines.
According to the ASCO and the NCCN guidelines, an NK1 receptor antagonist should be added to a prophylactic 2-drug regimen of 5-HT3 receptor antagonist plus dexamethasone for carboplatin-based chemotherapy.
If a prophylactic CINV regimen does not contain an NK1 receptor antagonist (ie, a MEC regimen), a single dose of granisetron extended-release injection or of palonosetron is the preferred 5-HT3 receptor antagonist, according to the NCCN guidelines.
“And if olanzapine wasn’t used on day one, consider it your breakthrough option,” he advised.
Recently Approved CINV Therapies
A novel formulation of granisetron extended-release injection provides sustained therapeutic drug levels for more than 5 days, and is now indicated for acute and delayed CINV associated with MEC and anthracycline-cyclophosphamide–based chemotherapy.
Oral netupitant plus palonosetron and intravenous (IV) fosnetupitant plus palonosetron are 2 fixed combination agents containing a long-acting NK1 receptor antagonist and a long-acting 5-HT3 receptor antagonist and are indicated for the prevention of acute and delayed CINV.
Rolapitant, which is indicated for the prevention of acute and delayed CINV, including but not limited to HEC, has the longest half-life of the available NK1 receptor antagonists, and has no drug interaction with dexamethasone.
Aprepitant emulsion is a surfactant-free, novel formulation that is better tolerated than fosaprepitant, and is indicated for the prevention of acute and delayed CINV associated with HEC or MEC regimens.
“Aprepitant emulsion [can be administered via] IV push, and it causes less infusion site reactions and less hypersensitivity [than fosaprepitant],” Dr Berger said. “So that’s a nice option.”
Controversies in Managing CINV
Controversy surrounds the optimal dose of dexamethasone, but according to Dr Berger, the dose can be individualized based on patient factors, concurrent medication use, side effects, and the chemotherapy regimen.
Controversy also surrounds carboplatin’s emetogenicity. Carboplatin’s area under the curve of ≥4 is currently considered HEC (according to the NCCN guidelines) or a unique category of MEC (according to the ASCO guidelines), and requires NK1 receptor antagonist or olanzapine prophylaxis. “Carboplatin is on the upper end of the MEC spectrum,” Dr Berger said.
The preferred 5-HT3 receptor antagonist when no NK1 receptor antagonist is used should be granisetron extended-release injection or palonosetron. When an NK1 receptor antagonist is used, no preferred 5-HT3 agent is currently available.
“But, ASCO redid their guidelines in 2017, before granisetron extended release [was approved], so this could change in the future,” Dr Berger noted. As of now, there is also no preferred NK1 receptor antagonist agent. “And there are no head-to-head trials that are even ongoing, that I’m aware of,” he added.
In terms of HEC regimens, olanzapine has been established as noninferior to an NK1 receptor antagonist regimen, and an NK1 receptor antagonist regimen added to olanzapine is better than an NK1 receptor antagonist regimen alone. Oncology pharmacists are also awaiting the results of a study investigating the addition of an NK1 to an olanzapine regimen compared with olanzapine alone. “So, this will become a little bit clearer as we go on,” Dr Berger noted.
The Role of the Pharmacist
According to Dr Berger, the goal for patients should always be grade 0 emesis and grade ≤1 nausea (ie, patient is still able to eat and drink). If in the first 24 hours the patient experiences grade 1 emesis or grade 2 nausea, escalate the acute CINV prevention.
“If you haven’t added olanzapine or an NK1, you should,” he advised. If patients have been adherent to their medications and still experience grade 1 emesis or grade 2 nausea in the delayed setting, escalate the delayed CINV prevention, by adding olanzapine or dexamethasone, or consider changing 5-HT3 receptor antagonist and/or NK1 receptor antagonist to a longer-acting agent.
Before devising a plan for an antiemetic regimen, pharmacists should consider any patient- and treatment-specific risk factors for CINV, as well as any other contributing factors for nausea and vomiting (ie, concomitant medications, disease level) he advised. Providers can also use the CINV tool kit offered on the HOPA website (www.hoparx.org).