CMS Reviewing Aprepitant NCD To Add Use With Moderately Emetogenic Chemo

The current Medicare Part B national coverage determination says use of the anti-nausea drug with highly emetogenic anti-cancer chemotherapy is reasonable and necessary; the National Comprehensive Cancer Network asks CMS to update the NCD based on evidence supporting use with moderately emetogenic agents.

CMS is reconsidering its national coverage determination on use of the oral antiemetic aprepitant in Medicare Part B.

The reconsideration will determine whether the NCD should support coverage of the drug’s use, in combination with a 5-HT3 antagonist and dexamethasone, in patients receiving moderately emetogenic anti-cancer chemotherapeutic (MEC) agents. The current aprepitant NCD, implemented in July 2005, says that coverage of aprepitant when used in combination with a 5-HT3 antagonist and dexamethasone is reasonable and necessary for patients who are receiving one or more highly emetogenic anti-cancer chemotherapeutic agents (Also see "Merck's Emend Granted Broad Coverage Under Medicare Part B" - Pink Sheet, 5 Apr, 2005.). FDA has since approved its use with MEC agents.

Aprepitant is marketed as Emend by Merck & Co. Inc. as well as in a generic version by Sandoz, that was approved Sept. 24, 2012. Medicare will cover an oral antiemetic under Part B if it is a full replacement for an intravenous antiemetic.

Aprepitant NCD Changes Requested By NCCN

• Expand the use of aprepitant in combination with dexamethasone and a 5-HT3 antagonist to include the patient population receiving anticancer chemotherapeutic agents currently considered moderately emetogenic. MEC agents classified using the Hesketh emetogenic classification system or listed in at least two published evidence-based guidelines include alemtuzumab, azacitidine, bendamustine, carboplatin, clofarabine, cyclophosphamide, cytarabine, daunorubicin, doxorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, and oxaliplatin.
• Expand coverage of aprepitant in combination with dexamethasone and a 5-HT3 antagonist for use with future chemotherapy agents classified as highly emetogenic or moderately emetogenic using the Hesketh emetogenic classification system or listed in at least two published evidence-based guidelines.
• Expand the current NCD acceptable list of 5-HT3 antagonists for use with aprepitant and dexamethasone to include palonosetron.
• Allow use of therapeutically equivalent doses of any available 5-HT3 antagonist, dexamethasone, and aprepitant formulations (oral, transdermal, intravenous).
• Allow for oral dexamethasone taken by the patient at home during the time period of chemotherapy administration.
• Allow for the intravenous administration of dexamethasone in place of oral dexamethasone.
• Allow for aprepitant in combination with 5-HT3 antagonists in patients shown to be dexamethasone (corticosteroid) intolerant or if the physician wishes to avoid dexamethasone (corticosteroids) because the patient is a diabetic.

Emend is approved in both capsule and intravenous formulations to prevent nausea and vomiting associated with highly or moderately emetogenic chemotherapies. The oral capsule formulations are also approved for post-operative nausea and vomiting.

The national coverage analysis (NCA) that could lead to a revised NCD will examine evidence on the drug’s use in combination with the other two drugs in patients receiving MEC agents. There is ample evidence for that use, given its approval by FDA in October 2005, all of the major drug compendia list it and it is included in a number of evidence-based guidelines for antiemesis published by health-care provider organizations, as pointed out in a letter from the National Comprehensive Cancer Network (NCCN) that requested the reconsideration.

The current NCD lists nine highly emetogenic products aprepitant can be used with, and NCCN’s letter lists 14 drugs classified as moderately emetogenic (see box).

An NCD sets a standard for local coverage determinations by Medicare contractors. While a local policy cannot be more restrictive than the NCD, it may be less restrictive, and in the case of chemotherapy, products are generally covered following uses listed in recognized compendia, including that published by NCCN.

NCCN wrote its letter to CMS Office of Clinical Standards and Quality Coverage and Analysis Group Director Louis Jacques in February 2012. The letter does not suggest that aprepitant coverage has been restricted due to the lack of an update, but indicates a desire to ensure that the NCD reflect developments since 2005. CMS has used NCDs to set nationwide Medicare policies on specific drugs in only a handful of closely-watched cases (Also see "A Closer Look: Decision For No Medicare NCD On ESAs In Renal Disease Would Be The Exception" - Pink Sheet, 28 Mar, 2011.).

CMS officially opened the NCD reconsideration on Oct. 1; public comments are due Oct. 31. CMS has set a due date of April 1, 2013 to issue a proposed decision memo, with a final decision expected by June 30, 2013, according to the national coverage analysis tracking sheet on CMS’ website.

In response to an inquiry, CMS’ lead analyst on the NCD, Cheryl Gilbreath, said the NCA would not involve review by the Medicare Evidence Development and Coverage Advisory Committee, nor would there be a public technology assessment. MEDCAC and TAs can be used in the NCA process along with a systematic review of evidence from the medical literature, often when the evidence is considered to be unclear or controversial, so skipping those elements suggests that CMS sees the reconsideration of aprepitant as a relatively straightforward affair.

While NCCN made a number of proposals for revising the aprepitant NCD (see box), the tracking sheet indicates that CMS is only considering the expanded use with MEC drugs at this time.

However, in the past, CMS has been flexible in making adjustments throughout the NCA process in response to public comments. Indeed, the aprepitant NCD was changed significantly from the proposal, which had suggested covering the drug only for patients who had failed on standard antiemetic regimens that did not include aprepitant.