Description
People with certain cancers may be given drugs (chemotherapy) to treat their disease. A side effect of many chemotherapy drugs is nausea and vomiting. Prevention of nausea/vomiting is the goal, and antiemetic drugs used for prophylaxis may vary by emetic risk of the chemotherapy drugs included in the regimen being used to treat the underlying cancer.

Policy 

Akynzeo (palonosetron/Fosnetupitant) injection
Aloxi (palonosetron) injection
Cinvanti (aprepitant) injectable emulsion
Emend (Fosaprepitant) injectable emulsion
Sustol (granisetron extended release) injection
 

Coverage of these drugs is provided when the criteria below is met. 

I. INDICATIONS
The indications below, including FDA-approved indications and compendial uses, are considered a covered benefit, provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

A. FDA-Approved Indications
Akynzeo (palonosetron/Fosnetupitant) injection
Akynzeo is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. 

Aloxi (palonosetron) injection
Aloxi is indicated for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately or highly emetogenic cancer chemotherapy.

Cinvanti (aprepitant) injectable emulsion
Cinvanti is indicated in combination with other antiemetic agents in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin, and moderately emetogenic chemotherapy.

Emend (Fosaprepitant) injectable emulsion
Emend is indicated in combination with other antiemetic agents in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin, and moderately emetogenic chemotherapy.

Kytril (granisetron) injection
Kytril is indicated in the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin.

Sustol (granisetron extended release) injection
Sustol is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.

Zofran (ondansetron) injection
Zofran is indicated for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately or highly emetogenic cancer chemotherapy. Zofran is also indicated for treatment of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen or daily fractions to the abdomen.

B. COMPENDIAL USES

Neurokinin-1 receptor antagonists (NK1 RA) — Cinvanti and Emend:
Acute and delayed emesis prevention with high emetic risk parenteral anticancer agents
Acute and delayed emesis prevention with moderate emetic risk parenteral anticancer agents in patient with additional risk factors

Serotonin receptor antagonists (5-HT3 RA) 
Aloxi
Acute and delayed emesis prevention with moderate or high emetic risk parenteral anticancer agents

Kytril, Sustol and Zofran:
Acute and delayed emesis prevention with moderate or high emetic risk parenteral or oral anticancer agents, or low to minimal emetic risk oral anticancer agents
Breakthrough treatment for anticancer therapy-induced nausea/vomiting

NK1 RA/5-HT3 RA combination
Akynzeo (palonosetron/Fosnetupitant) injection
Acute and delayed emesis prevention with high emetic risk parenteral anticancer agents
Acute and delayed emesis prevention with moderate emetic risk parenteral anticancer agents in patient with additional risk factors

C. CRITERIA FOR APPROVAL FOR ALL ANTIEMETICS

Criteria for the below is derived from NCCN Clinical Practice Guidelines Category 1, 2A and 2B recommendations for antiemesis and will be as follows:

• NK1 RA (Cinvanti, Emend)
  • Both of the following:
    • Prevention of chemotherapy-induced nausea and vomiting due to high emetic risk parenteral anticancer agents, AND
    • In combination with a 5HT3 RA

OR

• All of the following:
  • Prevention of chemotherapy-induced nausea and vomiting due to moderate emetic risk parenteral anticancer agents, AND
  • In combination with a 5HT3 RA, AND
  • At least one of the following risk factors for anticancer-agent induced nausea/vomiting:
    • Younger age ( < 55 years)
    • Female sex
    • Previous history of chemotherapy induced nausea or vomiting
    • Little or no previous alcohol use
    • History of motion sickness or morning sickness during pregnancy
    • Anxiety/high pretreatment expectation of nausea

• 5HT3 RA (Aloxi, Zofran, Kytril, Sustol)
  • Both of the following:
    • Prevention of chemotherapy-induced nausea and vomiting due to high emetic risk parenteral anticancer agents, AND
    • In combination with a NK1 RA

OR

Prevention of chemotherapy-induced nausea and vomiting due to moderate emetic risk parenteral anticancer agents

OR

• All of the following:
  • Prevention of chemotherapy-induced nausea and vomiting due to moderate emetic risk parenteral anticancer agents, AND
  • In combination with a NK1 RA, AND
  • At least one of the following risk factors for anticancer-agent induced nausea/vomiting:
    • Younger age ( < 55 years)
    • Female sex
    • Previous history of chemotherapy induced nausea or vomiting
    • Little or no previous alcohol use
    • History of motion sickness or morning sickness during pregnancy
    • Anxiety/high pretreatment expectation of nausea OR
  • Treatment of breakthrough nausea and/or vomiting due to anticancer agent(s)

• NK1 RA/5HT3 RA Combination (Akynzeo)
  • Prevention of chemotherapy-induced nausea and vomiting due to high emetic risk parenteral anticancer agents

OR

• All of the following:
  • Prevention of chemotherapy-induced nausea and vomiting due to moderate emetic risk parenteral anticancer agents, AND
  • At least one of the following risk factors for anticancer-agent induced nausea/vomiting:
    • Younger age ( < 55 years)
    • Female sex
    • Previous history of chemotherapy induced nausea or vomiting
    • Little or no previous alcohol use
    • History of motion sickness or morning sickness during pregnancy
    • Anxiety/high pretreatment expectation of nausea

National Comprehensive Cancer Network (NCCN) emetogenic risk designations:
High emetic risk ( > 90% frequency of emesis) parenteral anticancer agents

• AC combination defined as any chemotherapy regimen that contains an anthracycline and cyclophosphamide

• Carboplatin AUC ≥ 4

• Carmustine > 250 mg/m2

• Cisplatin

• Cyclophosphamide > 1500 mg/m2

• Dacarbazine

• Doxorubicin ≥ 60 mg/m2

• Epirubicin > 90 mg/m2

• Ifosfamide ≥ 2 g/m2 per dose

• Mechlorethamine

• Melphalan ≥ 140 mg/m2

• Sacituzumab govitecan-hziy

• Streptozocin

Moderate emetic risk ( > 30% – 90% frequency of emesis) parenteral anticancer agents

• Aldesleukin > 12 – 15 million IU/m2

• Amifostine > 300 mg/m2

• Amivantamab-vmjw

• Azacitidine

• Bendamustine

• Busulfan

• Carboplatin AUC < 4

• Carmustine ≤ 250 mg/m2

• Clofarabine

• Cyclophosphamide ≤ 1500 mg/m2

• Cytarabine > 200 mg/m2

• Dactinomycin

• Daunorubicin

• Dual-drug liposomal encapsulation of cytarabine and daunorubicin

• Dinutuximab

• Doxorubicin < 60 mg/m2

• Epirubicin ≤ 90 mg/m2

• Fam-trastuzumab deruxtecan-nxki

• Idarubicin

• Ifosfamide < 2 g/m2 per dose

• Irinotecan

• Irinotecan (liposomal)

• Lurbinectedin

• Melphalan < 140 mg/m2

• Methotrexate ≥ 250 mg/m2

• Naxitamab-gqgk

• Oxaliplatin

• Romidepsin

• Temozolomide

• Trabectedin

References

1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Antiemesis. v2.2022. Accessed April, 8, 2022.

2. Akynzeo (fosnetupitant and palonosetron) [prescribing information]. Iselin, NJ: Helsinn Therapeutics (US), Inc; January 2021. Accessed April 8, 2022.

3. Aloxi (palonosetron) [prescribing information]. Woodcliff Lake, NJ: Eisai, Inc; December 2015. Accessed April 8, 2022.

4. Ondansetron [prescribing information]. Philadelphia, PA: Lannett Company, Inc; June 2010. Accessed April 8, 2022.

5. Cinvanti (aprepitant) [prescribing information]. San Diego, CA: Heron Therapeutics; March 2022. Accessed April 8, 2022

6. Granisetron [prescribing information]. Lake Zurich, IL: Fresenius Kabi; February 2017. Accessed April 8, 2022

7. Sustol (granisetron extended release) [prescribing information]. San Diego, CA: Heron Therapeutics; May 2017. Accessed April 8, 2022

8. Emend (fosaprepitant) [prescribing information]. Whitehouse Station, NJ: Merck and Co., Inc.; March 2018. Accessed April 8, 2022

Coding Section

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This medical policy was developed through consideration of peer-reviewed medical literature generally recognized
by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice
and accepted standards of medical practice in this community, Blue Cross Blue Shield Association
technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to
federal regulations, other plan medical policies, and accredited national guidelines.

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