Subject:
Pemetrexed Disodium (Alimta®)
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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Pemetrexed disodium (Alimta) is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes during cellular replication. Specifically, pemetrexed inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase, which are folate-dependent enzymes required for the production of thymidine and purine nucleotides.
Pemetrexed disodium is marketed as Alimta by Eli Lilly and Company.
In February 2004, the FDA approved Alimta for combination therapy with cisplatin for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer, as a single-agent for the treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy, and in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. Subsequent approval by the FDA in July 2009 expanded the initial indications to the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
Non-small cell lung cancer is commonly classified as squamous cell carcinoma, large cell carcinoma, or adenocarcinoma. Currently, Alimta is not indicated for the treatment of squamous cell carcinoma.
In June 2018, the FDA granted approval for Alimta in combination with carboplatin and Keytruda (pembrolizumab) for the initial treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), irrespective of PD-L1 expression status. This indication is approved under accelerated approval based on tumor response rate and progression-free survival of Keynote-201 study. The study included 123 previously untreated patients with locally advanced or metastatic nonsquamous NSCLC with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations and irrespective of PD-L1 expression status. The triplet combination of Alimta and carboplatin with pembrolizumab (n=60) demonstrated a statistically significant improvement in objective response rate (ORR) versus Alimta plus carboplatin alone (n=63) (55% vs 29%; all responses were partial) (estimated difference, 26%; 95% confidence interval [CI], range of 42-68 for triplet and range of 18-41 for ALIMTA plus carboplatin; P=0.0032), and PFS (HR=0.53; 95% CI, 0.31-0.91, P=0.0205). Median PFS was 13.0 months for triplet and 8.9 months for Alimta plus carboplatin (range of 8.3-NE for triplet and 4.4-10.3 for Alimta plus carboplatin). Continued approval for this indication may be contingent upon verification and descriptrion of clinical benefit in the confirmatory trials.
[INFORMATIONAL NOTE: The FDA-approved Alimta (pemetrexed) package insert has the following warnings and precautions:
· Premedication: patients should receive folic acid, vitamin B12 and corticosteroids. As premedication to reduce instances of treatment related hematologic toxicity, GI toxicity, and cutaneous adverse events
· Bone Marrow Suppression: myelosuppression is usually the dose-limiting toxicity and may require dose reductions for subsequent cycles
· Renal Function: Alimta is eliminated unchanged in the urine. Decreased renal function will result in increased AUC; administration in patients with a CrCl of less than 45ml/min has not been studied and administration to these patients is not recommended
· Hepatic Function Impairment: dose adjustments based on hepatic impairment during treatment are required.
· Fertility Impairment: administration in mice at sub-therapeutic doses resulted in reduced fertility, hypospermia and testicular atrophy.
· Children: safety and efficacy in children has not been established.]
Policy:
Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.
The requirements of the Horizon BCBSNJ Pemetrexed Disodium (Alimta®) 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).
I. 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.
II. Pemetrexed (Alimta) is medically necessary for the following FDA-approved indications:
A. Nonsquamous Non-Small Cell Lung Cancer
- In combination with cisplatin for the initial treatment of patients with locally advanced or metastatic disease
- As a single agent, for the maintenance treatment of patients with locally advanced or metastatic disease which has not progressed after four cycles of platinum-based first-line chemotherapy
- As a single-agent for the treatment of patients with recurrent, metastatic nonsquamous non-small cell lung cancer after prior chemotherapy
- In combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous NSCLC, with no EGFR or ALK genomic tumor aberrations
B. Mesothelioma: in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are not candidates for curative surgery
III. When medical necessity criteria are met, pemetrexed (Alimta) will be approved for six (6) months based on FDA recommendations if lab results confirm that members have:
- Absolute Neutrophil Count (ANC) ≥ 1500 cells/mm
- Platelets ≥ 100,000 cells/mm3
- Creatinine Clearance (CrCl) ≥ 45 mL/min:
A. Nonsquamous non-small cell lung cancer and malignant pleural mesothelioma (combination therapy with cisplatin):
- The recommended dose of pemetrexed is 500 mg/m2 on Day 1 of each 21-day cycle
[INFORMATIONAL NOTE: Alimta should be infused intravenously over 10 minutes. The recommended dose of cisplatin is 75 mg/m2 infused over 2 hours starting 30 minutes after Alimta infusion. Patients should be adequately hydrated before and after treatment.]
B. Nonsquamous non-small cell lung cancer following first-line or second line therapy (single agent)
- The recommended dose is 500 mg/m2 on Day 1 of each 21-day cycle
C. Nonsquamous non-small cell lung cancer as first-line therapy (combination with carboplatin and pembrolizumab):
- The recommended dose is 500 mg/m2 on Day 1 of each 21-day cycle
[INFORMATIONAL NOTES:
Alimta should be infused intravenously over 10 minutes prior to carboplatin on Day 1 of each 21-day cycle for 4 cycles.
Following platinum-based therapy, Alimta may be administered as maintenance therapy, alone or with pembrolizumab, until disease progression or unacceptable toxicity.
Pembrolizumab should be administered prior to Alimta when given on the same day. ]
[INFORMATIONAL NOTE: Alimta may require dose adjustments at the start of a subsequent cycle based on nadir hematologic counts or maximum non hematologic toxicity from the preceding treatment cycle. Treatment can also be delayed to allow recovery time. Based on the FDA approved package insert, adjustments are recommended as follows:
Table 1: Recommended Dosage Modifications for Adverse Reactionsa |
 |
| Toxicity in Most Recent Treatment Cycle | ALIMTA Dose Modification for Next Cycle |
| Myelosuppressive toxicity |
ANC less than 500/mm3 and platelets greater than or equal to 50,000/mm3
OR
Platelet count less than 50,000/mm3 without bleeding. | 75% of previous dose |
| Platelet count less than 50,000/mm3 with bleeding | 50% of previous dose |
| Recurrent Grade 3 or 4 myelosuppression after 2 dose reductions | Discontinue |
| Non-hematologic toxicity |
Any Grade 3 or 4 toxicities EXCEPT mucositis or neurologic toxicity
OR
Diarrhea requiring hospitalization | 75% of previous dose |
| Grade 3 or 4 mucositis | 50% of previous dose |
| Renal toxicity | Withhold until creatinine clearance is 45 mL/min or greater |
| Grade 3 or 4 neurologic toxicity | Permanently discontinue |
| Recurrent Grade 3 or 4 non-hematologic toxicity after 2 dose reductions | Permanently discontinue |
| Severe and life-threatening Skin Toxicity | Permanently discontinue |
| Interstitial Pneumonitis | Permanently discontinue |
a National Cancer Institute Common Toxicity Criteria for Adverse Events version 2 (NCI CTCAE v2).
IV. Continued therapy with pemetrexed (Alimta) will be considered biannually if:
- Member continues to meet initial review criteria including lab requirements; AND
- Tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
- Absence of unacceptable toxicity from the drug (e.g.: severe bone marrow suppression, renal insufficiency, severe vomiting, bullous and exfoliative skin toxicity, interstitial pneumonitis).
[INFORMATIONAL NOTE: Complete blood counts (CBC) should be performed on all patients receiving Alimta. Patients should not begin a new cycle of treatment unless the ANC is ≥1500 cells/mm3, the platelet count is ≥100,000 cells/mm3, and creatinine clearance is ≥45 mL/min. Periodic chemistry tests should be performed to evaluate renal and hepatic function.]
V. Pemetrexed (Alimta) 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 - pemetrexed. Available at: [https://www.nccn.org/professionals/drug_compendium/content/].
VI. Other uses of pemetrexed (Alimta) are considered investigational including, but not limited to
- squamous cell non-small cell lung cancer
- small cell lung cancer
- central nervous system lymphoma
- head and neck cancer
- nasopharyngeal neoplasms
- breast cancer
- pancreatic cancer
- esophageal carcinoma
- acute leukemia (e.g., acute myeloid leukemia and acute lymphocytic leukemia)
- choriocarcinoma
- colorectal cancer
- gastric cancer
- cervical cancer
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical 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:
Pemetrexed Disodium (Alimta)
Alimta (Pemetrexed Disodium)
References:
1. AHFS Drug Information. American Society of Health-System Pharmacists, Inc. 2013.
2. Alimta® (Pemetrexed disodium) Prescribing Information. Eli Lilly and Company. Indianapolis, IN: January 2019.
3. "Non-small cell lung cancer treatment - National Cancer Institute". http://www.cancer.gov/CANCERTOPICS/PDQ/TREATMENT/NON-SMALL-CELL-LUNG/PATIENT. Retrieved 2010-08-02 2013-12-20.
4. Vincent MD. Optimizing the management of advanced non-small-cell lung cancer: a personal view. Curr Oncol 2009; 16: 9-21.
5. Zinner RG, Novello S, Peng G, Herbst R, Obasaju C, Scagliotti G. Comparison of patient outcomes according to histology among pemetrexed-treated patients with stage IIIB/IV non-small-cell lung cancer in two phase II trials. Clin Lung Cancer 2010;11:126-31.
6. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. v1.2018. Available at http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf
7. Pemetrexed. National Comprehensive Cancer Network: Drugs and Biologics Compendium. [Available at http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=44 (Accessed 01/04/2019 12/16/2019]
8. ODwyer PJ, Nelson K, Thornton DE. Overview of phase II trials of MTA in solid tumors. Semin Oncol. 1999; 26: 99-104
9. Vogelzang NJ, Rusthoven JJ, Symanowski K, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003; 21: 2636-44
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
* CPT copyright only 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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