Current Strategies in the Management of CINV

The oncology pharmacist plays an invaluable role in the management of chemotherapy-induced nausea and vomiting (CINV). However, as the pipeline for new anticancer drugs continues to expand, the pipeline for novel antiemetics appears to be drying up, underlining the importance of the pharmacist’s knowledge of currently 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,” he noted. It is up to the pharmacist to guard against over- or underutilization of antiemetics, while also being knowledgeable concerning drug properties, drug–drug interactions, clinical trial results, practice guidelines, cost, and potential for patient nonadherence, as these factors all play a role in antiemetic selection.

Dr Berger provided HOPA attendees with an overview of current antiemetic guidelines, recently approved agents, and controversies surrounding the management of CINV.

Assessing Emetogenic Risk

A risk assessment for CINV should be completed for each patient before the start of anticancer therapy and before any subsequent chemotherapy cycles. Prophylactic medications should be scheduled throughout the period of risk—4 days for a single-day highly emetogenic chemotherapy (HEC) regimen and 3 days for moderately emetogenic chemotherapy (MEC). Pharmacists should also plan to have a breakthrough agent available from a different pharmacologic class, Dr Berger 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 single-agent chemotherapy, but when a multiagent regimen is used, it should be based on the drug in the regimen with the highest emetic risk. For example, cisplatin (high) plus etoposide (low) would be HEC, whereas oxaliplatin (moderate) plus fluorouracil (5-FU) (low) plus leucovorin (minimal) would be MEC. In the case of 2 moderately emetogenic drugs (ie, an anthracycline plus cyclophosphamide), the regimen should be considered HEC.

According to Dr Berger, nausea remains a more significant problem than vomiting. Many physicians and nurses think CINV is fairly well controlled, but patient perceptions tend to be different. A 2015 HOPA survey that assessed perceptions about nausea and vomiting among patients receiving chemotherapy revealed numerous misconceptions, including the myth that nausea and vomiting indicate that the chemotherapy is working, and the belief that CINV is simply to be expected. Patients also commonly think that as long as they are not vomiting, their CINV is being controlled.1

Current Guidelines

Olanzapine, an atypical antipsychotic agent, has been found to improve outcomes when added to a prophylactic regimen of a neurokinin 1 (NK1) receptor antagonist (RA) plus a serotonin (5-HT3) RA plus dexamethasone and is now considered a standard-of-care option for patients treated with cisplatin-based and other HEC regimens, according to guidelines from the American Society of Clinical Oncology (ASCO)2 and the National Comprehensive Cancer Network (NCCN).3 These guidelines also recommend that an NK1 RA be added to a prophylactic regimen of a 5-HT3 RA plus dexa­methasone for patients receiving carboplatin-­based chemotherapy.

If a prophylactic antiemetic regimen does not contain an NK1 RA, a single dose of granisetron (Sustol) extended­release injection or intravenous (IV) palonosetron (Aloxi) are the preferred 5-HT3 RAs, per NCCN guidelines.

“And if olanzapine wasn’t used on day one, consider it your breakthrough option,” Dr Berger advised.

Recently Approved Agents

Subcutaneous granisetron extended-release injection is a new formulation that provides sustained therapeutic drug levels for >5 days; this agent is now indicated for CINV associated with MEC and anthracycline­cyclophosphamide–based chemotherapy. Oral netupitant/palonosetron (Akynzeo) and IV fosnetupitant/palonosetron (Aky­nzeo) are both fixed-combination products containing a long-acting NK1 RA and a long-acting 5-HT3 RA, and are indicated for the prevention of acute and delayed CINV.

Rolapitant (Varubi), 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 RAs, and has no drug–drug interactions with dexamethasone.

Aprepitant injectable emulsion (Cinvanti) is a surfactant-free, novel formulation that appears to be better tolerated than IV fosaprepitant (Emend), and is indicated for the prevention of acute and delayed CINV associated with HEC and MEC.

“Aprepitant emulsion [can be administered via] IV push, and it causes less infusion site reactions and less hypersensitivity [than fosaprepitant],” he noted. “So that’s a nice option.”

Ongoing Controversies

Controversy continues over the optimal dose of dexamethasone, but the dose can be individualized based on patient-specific factors, concurrent medications, side effects, and chemotherapy regimen, according to Dr Berger.

More controversy surrounds carboplatin’s emetogenicity. Carboplatin area under the curve of ≥4 is currently considered HEC (according to NCCN guidelines), or a unique category of MEC (according to ASCO guidelines), and requires prophylaxis with an NK1 RA or olanzapine.

“Carboplatin is on the upper end of the MEC spectrum,” he said.

The preferred 5-HT3 RA when no NK1 RA is used is granisetron extended-release injection or palonosetron. When an NK1 RA is used, there is no preferred 5-HT3 RA agent, yet.

“But, ASCO revised 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 RA agent.

In terms of HEC regimens, olanzapine has been established as noninferior to an NK1 RA regimen, and an NK1 RA regimen added to olanza­pine is better than an NK1 RA regimen alone.

The Pharmacist’s Role

According to Dr Berger, the goal for patients should always be grade 0 emesis and ≤grade 1 nausea (ie, patients are still able to eat and drink). If, in the first 24 hours of treatment, patients experience grade 1 emesis or grade 2 nausea, acute prevention should be escalated.

“If you haven’t added olanzapine or an NK1 RA, you should,” he advised. If a patient has been adherent to their medications and experiences grade 1 emesis or grade 2 nausea in the delayed setting, escalate delayed prevention and add olanzapine or dexamethasone, or consider changing the 5-HT3 RA and/or NK1 RA 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 (eg, concomitant medications, disease), Dr Berger noted. Providers can also use the CINV tool kit offered on the HOPA website.


References

  1. Hematology/Oncology Pharmacy Association. Myths and facts about CINV. www.hoparx.org/images/hopa/resource-library/patient-education/Myths_and_Facts_about_CINV.pdf. Accessed April 19, 2019.
  2. Hesketh PJ, Bohlke K, Kris MG. Antiemetics: American Society of Clinical Oncology clinical practice guideline update summary. J Oncol Pract. 2017;13:825-830.
  3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Antiemesis. Version 1.2019. February 28, 2019. www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed April 22, 2019.

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