Subject:
Olaratumab (Lartruvo)
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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Soft Tissue Sarcomas are a heterogeneous group of rare malignant tumors. It is a type of cancer that develops from certain tissues, like bone or muscle. They can be found in any part of the body but most people develop them in the arms or legs. There are many types of soft tissues tumors and not all of them are cancerous. There are more than 50 different types of soft tissue sarcomas which include kaposi sarcoma and clear cell sarcoma. In the United States, the annual incidence of STS is estimated at 3.4 per 100,000 people. The incidence is higher in white males. The causes of STS is unknown, majority of cases arise without an obvious cause. The NCCN guidelines which was recently published in 2016 do not provide specific recommendations in regards to which therapy to use first in most cases of STS.
Lartruvo (olaratumab) injection is a platelet-derived growth factor receptor alpha (PDGFR-á) blocking antibody indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy surgery.
Lartruvo was approved under accelerated approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial. The efficacy of Lartruvo was demonstrated in an open-label, randomized, active-controlled study. Eligible patients were required to have soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy, a histologic type of sarcoma for which an anthracycline-containing regimen was appropriate but had not been administered, ECOG PS of 0-2, and tumor specimen available for assessment of PDGFR-á expression by an investigational use assay. One hundred and thirty-three (133) patients were randomized (1:1) to receive Lartruvo in combination with doxorubicin or doxorubicin as a single agent. Lartruvo was administered at 15 mg/kg as an intravenous infusion on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. All patients received doxorubicin 75 mg/m2 as an intravenous infusion on Day 1 of each 21-day cycle for a maximum of eight cycles and were permitted to receive dexrazoxane prior to doxorubicin in Cycles 5 to 8. Patients randomized to receive doxorubicin as a single agent were offered Lartruvo at the time of disease progression. The efficacy outcome measures were overall survival (OS), and progression-free survival (PFS) and objective response rate (ORR). Median OS was improved by 11.8 months in patients randomized to receive Lartruvo plus doxorubicin compared to patients randomized to doxorubicin alone, and was statistically significant. Median OS was 26.5 months on the Lartruvo-doxorubicin arm compared to 14.7 months on the doxorubicin-only arm. Patients treated on the Lartruvo and doxorubicin arm achieved 8.2 months of median PFS compared to 4.4 months on the doxorubicin-only arm, based on independent review. The number of events at the time of analysis was 37 (56%) on the Lartruvo-doxorubicin arm and 34 (51%) on the doxorubicin-only arm. The number of deaths at the time of analysis was 39 (59%) on the Lartruvo-doxorubicin arm and 52 (78%) on the doxorubicin-only arm. Objective response rate (ORR), based on independent review and defined as complete response (CR) plus partial response (PR), was also assessed with an ORR of 18.2 percent on the Lartruvo-doxorubicin arm and 7.5 percent on the doxorubicin-only arm.
In April 2019, Lilly announced it will pull Lartruvo from the US market after failure of phase III ANNOUNCE clinical trial where Lartrivo did not improve patient survival. The trial was a randomized, double-blind, Phase III of Lartruvo in combination with doxorubicin, followed by Lartruvo alone compared to doxorubicin plus placebo followed by placebo in patients with advanced or metastatic STS. The two primary endpoints were overall survival (OS) in the intent-to-treat (ITT) population and OS in the leiomyosarcoma (LMS) sub-population. Lartruvo was approved in the U.S in 2016 on the basis of a smaller mid-stage clinical trial under an accelerated approval program. The results of the ANNOUNCE trial were expected to verify the data but did not. The company is working on an access program that will give current patients and their physicians access to the drug with limited interruption after it is withdrawn from the market. Those patients will be informed of the risks of the drug and the results of the ANNOUNCE trial. No new patients will receive the drug except via ongoing clinical trials.
On October 2, 2019, the U.S Food & Drug Administration (FDA) issued an alert stating there has been a market withdrawal of Lartruvo. As per the FDA, there is no safety or quality issue related to the withdrawal.
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
The requirements of the Horizon BCBSNJ Olaratumab (Lartruvo) 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. Lartruvo (olaratumab) is medically necessary for the following FDA approved indication when ALL of the following criteria are met:
A. Retrospective requests
- Members who have soft tissue sarcoma (STS) with histologic subtype for which an anthracycline-containing regimen is appropriate but the member has no prior exposure to anthracycline and which is not amenable to curative treatment with radiotherapy or surgery and to be used in combination with doxorubicin AND
- Member is over the age of 18 AND
- Member has an ECOG performance score of 0-2 AND
- Member has normal coagulation, hematologic, hepatic and renal function AND
- Member has left ventricular ejection fraction (LVEF) ≥ 50 % at baseline AND
- Member does not have any of the following:
- Human immunodeficiency virus (HIV) infection
- Kaposi sarcoma
2. Lartruvo (olaratubmab) is considered not medically necessary for the treatment of STS in new starts or for continuation of therapy
[INFORMATIONAL NOTE: Based on the recently completed results of the ANNOUNCE phase 3 soft tissue tissue sarcoma study of Lartruvo in combination with doxorubicin, which did not confirm clinical benefit, specifically improvement in overall survival, the FDA recommends that patients who are currently receiving Lartruvo should consult with their healthcare provider about whether to remain on the treatment. The FDA also recommends that Lartruvo should not be initiated in new patients outside of an investigational study.
As of 7/31/19, all requests for Lartruvo will be handled by the manufacturer through the Lartruvo Patient Access Program. Only patients who are receiving Lartruvo as continuation therapy are eligible for this program, although new patients will be evaluated on a case-by-case basis. Enrollment and access to the drug will be provided free of charge for eligible patients.
As of 10/2/19, the FDA issued an alert stating Lartruvo has been withdrawn from the market.]
[INFORMATIONAL NOTE: Based on the pivotal trial for FDA approval of LARTRUVO, patients who were excluded had untreated central nervous system (CNS) metastases, unstable angina pectoris, angioplasty, cardiac stenting.]
3. When Lartruvo (olaratumab) is considered medically necessary, initial therapy will be approved for a period of 3 months at the following FDA-approved dose (for retrospective requests):
- 15 mg/kg as an intravenous infusion on Days 1 and 8 of each 21-day cycle
- First 8 cycles, Lartruvo should be administered with doxorubicin
[INFORMATION NOTE: Based on FDA approved package insert, premedication with diphenhydramine and dexamethasone intravenously, prior to Lartruvo on Day of cycle 1.]
4. Continuation of Lartruvo (olaratumab) will be approved every 3 months at the FDA-approved dose of 15 mg/kg as an intravenous infusion on Days 1 and 8 of each 21-day cycle if none of the following occurs:
- Unacceptable toxicity;
- Grade 3 or 4 infusion related reactions; OR
- Disease progression
[INFORMATIONAL NOTE: Based on the FDA approved package insert, for patients with neutropenic fever/infection or Grade 4 neutropenia lasting longer than 1 week, discontinue administration of Lartruvo until the absolute neutrophil count is 1,000 /microliter or greater and then permanently reduce the dose to 12 mg/kg.]
5. Lartruvo (olaratumab) is considered investigational for all other indications.
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage 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:
Olaratumab (Lartruvo)
Lartruvo (Olaratumab)
Soft Tissue Sarcomas, Olaratumab (Lartruvo) for
References:
1. Lartruvo (olaratumab) [Prescribing Information]. Eli Lilly Company. November 2016.
2. Sarcoma: Adult Soft tissue Sarcoma. American Cancer Society. November 2016. Available at: http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-soft-tissue-sarcoma
3. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology, soft tissue sarcoma. Version 2.2018. March 27.2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Accessed May 2018.
4. Tap WD, Jones RL, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomized phase 2 trial. Lancet. 2016;388(10043):488-97.
5. National Comprehensive Cancer Network.Uterine Neoplasms. Version 2.2018. May 25, 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed May 2018.
6. Eli Lilly. Lilly to Establish an access program for patients as it prepares to withdraw Lartruvo from the global market. Available at https://investor.lilly.com/news-releases/news-release-details/lilly-establish-access-program-patients-it-prepares-withdraw. Accessed May 2019
7. FDA Drug Shortage. Current and Resolved Drug Shortages and Discontinuations Reported to FDA. Olaratumab (Lartruvo) injection. Available at: https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Olaratumab (Lartruvo) Injection&st=d
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
J9285
* CPT only copyright 2019 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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