Subject:
Yondelis (Trabectedin)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Yondelis (trabectedin) is an alkylating drug approved for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Trabectedin ultimately causes a disruption in the tumor cell cycle and cell death by initiating a cascade of events triggered by the binding of guanine resides in the minor groove of DNA that results in bending the DNA helix toward the groove.
Yondelis has been approved in Europe for the treatment of soft tissue sarcoma in 2007, and subsequently for the treatment of ovarian cancer in 2008. FDA approval was issued in October of 2015 for the treatment of liposarcoma and leiomyosarcoma only. Due to the low incidence of these types of cancers, Yondelis has orphan drug designation in the United States.
In a randomized, open-labeled trial of patients with metastatic or recurrent leiomyosarcoma or liposarcoma (N=518), treatment with trabectedin significantly improved progression free survival (4.2 vs 1.5 months) compared with dacarbazine; however, a significant benefit was not observed for overall survival (13.7 vs 13.1 months), objective response rate (7% vs 6%), or duration of response (6.9 vs 4.2 months). Eligible subjects had unresectable, locally advanced, or metastatic disease and had received prior treatment with an anthracycline- and ifosfamide-containing regimen, or an anthracycline-containing regimen.
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
The requirements of the Horizon BCBSNJ Yondelis (Trabectedin) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).
1. Treatment with trabectedin (Yondelis) is considered medically necessary for the treatment of unresectable or metastatic liposarcoma or leiomyosarcoma when ALL of the following criteria are met:
a. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis; AND
b. Member is at least 18 years and older; AND
c. Documented failure of prior anthracycline-containing chemotherapy or intolerance, AND
d. Baseline left ventricular ejection fraction (LVEF) is within normal limits, AND
e. The patient does NOT have any of the following:
i. Significant chronic liver disease such as cirrhosis or active hepatitis OR severe hepatic impairment (bilirubin levels above 3 times the upper limit of normal, and any AST and ALT)
ii. Diagnosis of NYHA class II – IV heart failure
[INFORMATIONAL NOTE: Based on the pivotal trial for FDA approval of Yondelis, patients were excluded who had CNS metastasis, significant chronic liver disease, and a diagnosis of NYHA class II-IV heart failure. Yondelis may result in hepatotoxicity, and fatal or severe cardiomyopathy can occur. As a result, withhold Yondelis in patients with left ventricular dysfunction.]
2. Trabectedin (Yondelis) is considered medically necessary for off-label indications that have in effect a rating of ‘Category 1’ or ‘Category 2A’ in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - trabectedin. Available at: https://www.nccn.org/store/login/login.aspx?ReturnURL=/professionals/drug_compendium/content
3. When trabectedin (Yondelis) is considered medically necessary, initial therapy will be approved for a period of 6 months at the FDA-approved dose of 1.5mg/m2 body surface area as a 24-hour intravenous infusion, every 3 weeks through a central venous line.
[INFORMATION NOTE: : As per the FDA labeled package insert: the recommended dose is 0.9 mg/m2 in patients with moderate hepatic impairment (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal, and AST and ALT less than 8 times the upper limit of normal). Do not administer YONDELIS to patients with severe hepatic impairment (bilirubin levels above 3 times the upper limit of normal, and any AST and ALT)
Premedication: dexamethasone 20mg IV, 30 minutes before each infusion.
Assess neutrophil count prior to administration of each dose of Yondelis and periodically throughout the treatment cycle. Withhold or reduce dose of Yondelis based on severity of adverse reaction.
Assess creatinine phosphokinase levels prior to each administration of Yondelis. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction
Assess LVEF by echocardiogram (ECHO) or multigated acquisition (MUGA) scan before initiation of YONDELIS and at 2- to 3-month intervals thereafter until YONDELIS is discontinued. Discontinue treatment with YONDELIS based on severity of adverse reaction.]
4. Continuation of trabectedin (Yondelis) will be approved annually at the FDA-approved dose of 1.5mg/m2 as a 24-hour intravenous infusion every 3 weeks if ALL of the following criteria are met:
a. Member continues to meet the initial criteria, AND
b. There is clinical evidence of tumor response with stabilization of disease or decrease in size of tumor or tumor spread, AND
c. There are no unacceptable toxicities (e.g.: cardiomyopathy, rhabdomyolysis, hepatotoxicity, severe hepatic impairment, capillary leak syndrome, severe neutropenia, neutropenic sepsis, etc.), AND
d. Left ventricular ejection fraction has not had an absolute decrease from baseline of at least 15% or below the lower limit of normal with an absolute decrease of at least 5% and the patient does not have symptomatic LVEF changes
[INFORMATIONAL NOTE: Based on the FDA approved package insert, once reduced, the dose of Yondelis should not be increased in subsequent treatment cycles. The dose reductions for Yondelis in patients with normal hepatic function are:
• First dose reduction: Yondelis 1.2 mg/m2 every 3 weeks
• Second dose reduction: Yondelis 1.0 mg/m2 every 3 weeks
Permanently discontinue Yondelis for: Persistent adverse reactions requiring a delay in dosing of more than 3 weeks, Adverse reactions requiring dose reduction following Yondelis administered at 1.0mg/m, Severe liver dysfunction (all of the following: Bilirubin 2x ULN, AST or ALT > 3x ULN, Alk Phos < 2x ULN), exacerbation of liver dysfunction in patients with pre-existing moderate hepatic impairment, capillary leak syndrome, rhabdomyolysis, Grade 3 or 4 cardiac adverse events (AEs) indicative of cardiomyopathy or for subjects with an LVEF that decreases below the lower limit of normal.]
5. Trabectedin (Yondelis) is considered investigational for all other indications, including but not limited to ovarian cancer, malignant pleural mesothelioma, prostate cancer, refractory chronic lymphocytic leukemia, refractory small lymphocytic lymphoma, pancreatic cancer, and breast cancer.
Medicare Coverage
There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Yondelis (Trabectedin)
Trabectedin (Yondelis)
References:
1. Yondelis [Prescribing Information]. Janssen. January 2019.
2. Trabectedin and its Potential in the Treatment of Soft Tissue Sarcoma. Cassier et al. Clinical Risk Management. Published Feb 2008. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503645/
3. Sarcoma: Adult Soft Tissue Sarcoma. American Cancer Society. Revised March 2015. Available from: http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-soft-tissue-sarcoma
4. Mayo Clinic. Disease Conditions: Soft tissue sarcoma. Available at: http://www.mayoclinic.org/diseases-conditions/soft-tissue-sarcoma/basics/definition/con-20033386. Accessed: April 2015.
5. National Cancer Institute. Adult Soft Tissue Sarcoma Treatment (PDQ®). Available at: http://www.cancer.gov/cancertopics/pdq/treatment/adult-soft-tissue-sarcoma/HealthProfessional. Accessed: April 2015.
6. National Comprehensive Cancer Network: Drugs and Biologics Compendium. 2020. Available at https://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=428 [Accessed January 28, 2020]
7. ClinicalTrials.gov. Yondelis (trabectedin). Available at https://clinicaltrials.gov/ct2/results?cond=&term=yondelis&cntry=&state=&city=&dist=. Accessed January 2020.
8. National Comprehensive Cancer Network. Soft Tissue Sarcoma (Version 5.2019). https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Accessed January 28, 2020.
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
J9352
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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