Clinical UM Guideline
This document addresses fosaprepitant (Emend, Merck & Co., Inc., Whitehouse Station, NJ), a human substance P/neurokinin-1 (NK-1) receptor antagonist. Given intravenously (IV), fosaprepitant is used for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and moderately emetogenic cancer chemotherapy.
Fosaprepitant is considered medically necessary in combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and moderately emetogenic cancer chemotherapy.
Not Medically Necessary:
Fosaprepitant is considered not medically necessary for all other indications.
The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
Injection, fosaprepitant, 1 mg [Emend]
In situ neoplasms
Nausea and vomiting
Encounter for antineoplastic chemotherapy
Personal history of malignant neoplasm
Chemotherapy-induced nausea and vomiting is a known side effect of chemotherapy. There are three types of chemotherapy-induced nausea and vomiting: acute, occurring within the first 24 hours following chemotherapy; delayed, occurring more than 24 hours after chemotherapy; and anticipatory emesis, occurring prior to treatment as a conditioned response in those who have developed nausea and vomiting during previous chemotherapy. The goal of antiemetic therapy is the prevention and management of chemotherapy-induced nausea and vomiting.
Fosaprepitant (Merck & Co., Inc., Whitehouse Station, NJ) was initially approved by the United States (U.S.) Food and Drug Administration (FDA) in 2008. Fosaprepitant is given via IV in combination with other antiemetic agents for the prevention of nausea and vomiting associated with highly and moderately emetogenic chemotherapy. Fosaprepitant is given on the first day of chemotherapy. In 2016, the Product Information label for fosaprepitant was updated to note that the drug has not been studied for the treatment of established nausea and vomiting.
The National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines®, 2018) has defined chemotherapeutic agents as high emetic risk when they have a 90% or greater frequency of causing emesis. A moderate emetic risk is defined as 30%-90% frequency of causing emesis. NCCN includes category 1 recommendations for the use of fosaprepitant in those undergoing treatment with high or moderate emetic risk agents.
In 2016, Ruhlmann and associates, studied the use of fosaprepitant in the prevention of radiation induced nausea and vomiting. In a multinational, randomized, double-blind, placebo-controlled phase 3 trial, women with cervical cancer scheduled to receive radiotherapy and weekly cisplatin were randomized to receive either single doses of IV fosaprepitant (n=118) or a saline placebo (n=116) in combination with IV palonosetron and oral dexamethasone prior to cisplatin administration. The primary endpoint was the proportion of individuals with sustained no emesis after 5 weeks of treatment. Secondary endpoints measured the proportion of individuals with a complete response (no emesis and no use of rescue medications). The proportion of individuals with sustained no emesis at 5 weeks (competing risk analysis) was 48.7% (95% confidence interval [CI] 25.2–72.2) for the placebo group compared with 65.7% (95% CI, 42.2–89.2) for the fosaprepitant group. The overall complete response rate, defined as no emesis and no rescue medications, over the course of treatment was higher in the fosaprepitant group compared to the placebo group (24% in the fosaprepitant group compared to 14% in the placebo group; p=0.007). There were no serious adverse events which were considered drug related. The authors noted that future studies might explore newer NK-1 receptor antagonists other drugs which appear to be effective against chemotherapy-related nausea in addition to emesis.
A study by Saito and colleagues (2013) reported on the safety and efficacy of single-dose fosaprepitant following treatment with cisplatin. In this multicenter, placebo-controlled, double-blind, randomized parallel study, the control group (n=167) received intravenous (IV) placebo, granisetron and dexamethasone while the treatment group (n=173) received IV fosaprepitant, granisetron and dexamethasone in the intention-to-treat analysis. The primary endpoint was the percentage of participants who had a complete response (no emesis and no rescue therapy) over the entire treatment course. The percentage of participants with a complete response was 64% in the treatment group compared with 47% in the placebo group (p=0.0015). The fosaprepitant regimen was more effective than the control regimen in both the acute (0-24 hour post chemotherapy) phase (94% versus 81%, p=0.0006) and the delayed (24-120 hour post chemotherapy) phase (65% versus 49%, p=0.0025).
In a 2011 study by Grunberg and colleagues, fosaprepitant was compared to aprepitant, the oral form of fosaprepitant approved by the FDA in 2003. The authors sought to determine whether a single intravenous dose of fosaprepitant was non-inferior to a 3 day oral aprepitant regimen. The phase III, double-blind study included 2322 participants who were randomly assigned to one of two treatment arms: the fosaprepitant group (n=1147) or the aprepitant group (n=1175). The primary endpoint was complete response defined as no vomiting or retching with no rescue medication during overall phase, defined as 0 to 120 hours following initiation of chemotherapy. Secondary endpoints were the proportion of participants with complete response in the delayed phase defined as 25 to 120 hours following initiation of chemotherapy, and the proportion of participants with no vomiting in the overall phase. The participants completed a daily diary for 5 days following the start of chemotherapy and kept track of vomiting or retching episodes, the use of any rescue therapy, and nausea ratings. For the primary endpoint, 71.9% (95% CI, 69.1% to 74.5%) of participants in the fosaprepitant group reported complete response compared to 72.3% (95% CI, 69.6% to 74.9%) in the aprepitant group. For the secondary endpoint, 74.3% (95% CI, 71.6% to 76.9%) of participants reported complete response in the fosaprepitant group compared to 74.2% (95% CI, 71.6% to 76.8%) in the aprepitant group. For the secondary endpoint of no vomiting during overall phase, 72.9% (95% CI, 70.2% to 75.5%) of participants in the fosaprepitant group reported no vomiting compared to 74.6% (95% CI, 71.9% to 77.1%) in the aprepitant group, supporting the non-inferiority of intravenous fosaprepitant to oral aprepitant.
Emetogenic: Having the capacity to induce vomiting.
High risk: Emesis that has been documented to occur in more than 90% of patients.
Moderate risk: Emesis that has been documented to occur in 30% to 90% of patients.
Peer Reviewed Publications:
- Grunberg S, Chua D, Maru A, et al. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol–EASE. J Clin Oncol. 2011; 29(11):1495-1501.
- Ruhlmann CH, Herrstedt J. Fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther. 2012; 12(2):139-150.
- Ruhlmann CH, Christensen TB, Dohn LH, et al: Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol 2016; 17(4):509-518.
- Saito H, Yoshizawa H, Yoshimori K, et al. Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Ann Oncol. 2013; 24(4):1067-1073.
Government Agency, Medical Society, and Other Authoritative Publications:
- Emend® [Product Information], Whitehouse Station, NJ. Merck & Co., Inc.; August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022023s016lbl.pdf . Accessed on April 11, 2018.
- Fosaprepitant. In: DrugPoints System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated February 20, 2018. Available at: http://www.micromedexsolutions.com . Accessed on February 22, 2018.
- Fosaprepitant Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised March 5, 2017. Accessed on February 22, 2018.
- Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017; 35(28):3240-3261. Available at: http://ascopubs.org/doi/pdf/10.1200/JCO.2017.74.4789 . Accessed on April 11, 2018.
- National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium™ (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on April 11, 2018.
- NCCN Clinical Practice Guidelines in Oncology®. © 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on April 11, 2018.
- Antiemesis (V.1.2018). Revised March 14, 2018.
|Websites for Additional Information|
- American Cancer Society (ACS). Medicines to prevent and treat nausea and vomiting. Last reviewed: June 9, 2016. Available at: http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/nauseaandvomiting/nauseaandvomiting/nausea-and-vomiting-drugs . Accessed on April 10, 2018.
- National Cancer Institute. Nausea and Vomiting Related to Cancer Treatment (PDQ®). Updated on June 6, 2017. Available at: http://www.cancer.gov/about-cancer/treatment/side-effects/nausea/nausea-pdq . Accessed on April 10, 2018.
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
Medical Policy & Technology Assessment Committee (MPTAC) review.
Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Discussion, References and Websites sections.
Hematology/Oncology Subcommittee review. Updated Discussion, References and Websites sections.
Hematology/Oncology Subcommittee review. Updated Description, Discussion, Definitions, References and Websites sections. Removed ICD-9 codes from Coding section.
Hematology/Oncology Subcommittee review. Initial document development.
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Assistance Program Resources
The Merck Access Program (MAP) can contact insurers to obtain coverage and beneﬁts information for EMEND.
If a prior authorization is required, or for assistance in understanding if a prior authorization is required, MAP may be able to help.
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The appeal checklist and sample appeal letter below can help you to understand the documents and information that may be helpful when filing
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