BlueCross BlueShield of Tennessee Medical Policy Manual

Pemetrexed (Alimta®)

NDC CODE(S)

00002-7640-XX ALIMTA 100MG Solution Reconstituted (ELI LILLY & CO.)

00002-7623-XX ALIMTA 500MG Solution Reconstituted (ELI LILLY & CO.)

DESCRIPTION

Pemetrexed is a folate analog metabolic inhibitor.  It interferes with cell metabolic processes by disrupting the folate-dependent processes required for cell replication by inhibiting the biosynthesis of thymidine and purine nucleotides.  This prevents the formation of the DNA and RNA required for the growth and survival of both cancer and normal cells.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

Universal Criteria

Primary Central Nervous System (CNS) Lymphoma

Malignant Pleural* Mesothelioma (MPM)

*peritoneal, pericardial, and tunica vaginalis testis mesothelioma will be evaluated on a case-by-case basis

Non-Squamous Non-Small Cell Lung Cancer (NSNSCLC)

Used as subsequent therapy; AND

Used as maintenance therapy in patients who have achieved tumor response or stable disease following initial therapy; AND

* Note: If there is insufficient tissue to allow testing for all of the EGFR, ALK, ROS1, BRAF, NTRK1/2/3,  MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.

Thymomas/Thymic Carcinoma

Ovarian Cancer (epithelial ovarian/fallopian tube/primary peritoneal cancer)

 

Genomic Aberration/Mutational Driver Targeted Therapies

(Note: not all inclusive, refer to guidelines for appropriate use)

Sensitizing EGFR mutation-positive tumors

ù  Afatinib

ù  Erlotinib

ù  Dacomitinib

ù  Gefitinib

ù  Osimertinib

ALK rearrangement-positive tumors

ù  Alectinib

ù  Brigatinib

ù  Ceritinib

ù  Crizotinib

ù  Lorlatinib

ROS1 rearrangement-positive tumors

ù  Ceritinib

ù  Crizotinib

ù  Entrectinib

BRAF V600E-mutation positive tumors

ù  Dabrafenib ± Trametinib

ù  Vemurafenib

NTRK Gene Fusion positive tumors

ù  Larotrectinib

ù  Entrectinib

PD-1/PD-L1 expression-positive tumors (≥1%)

ù  Pembrolizumab

ù  Atezolizumab

ù  Nivolumab ± ipilimumab

MET Exon-14 skipping mutations

ù  Capmatinib

ù  Crizotinib

RET rearrangement-positive tumors

ù  Selpercatinib

ù  Cabozantinib

ù  Vandetanib

RENEWAL CRITERIA

Continuation of Maintenance Therapy for Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

MPM

Thymomas/Thymic Carcinoma

DOSAGE/ADMINISTRATION

INDICATION

DOSE

Non-Squamous NSCLC

Administer 500 mg/m2 intravenously every 21 days, until disease progression or unacceptable toxicity

Malignant Pleural Mesothelioma

Administer 500 mg/m2 intravenously every 21 days

ù  For 6 cycles only when used in combination with platinum therapy

ù  and bevacizumab

ù  All others until disease progression or unacceptable toxicity

Primary CNS Lymphoma, Ovarian Cancer

Administer 900 mg/m2 intravenously every 21 days, until disease progression or unacceptable toxicity

Thymomas/Thymic Carcinoma

Administer 500 mg/m2 intravenously every 21 days for a maximum of 6 cycles in absence of disease progression or unacceptable toxicity

·         Supplement with oral folic acid and intramuscular vitamin B12

·         Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration in patients with CrCl <80 mL/min.

·         Do not dose in patients with CrCl <45 mL/min

 

LENGTH OF AUTHORIZATION

 

Coverage will be provided for six months and may be renewed unless otherwise specified.

DOSAGE LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

1.     Alimta [package insert]. Indianapolis, IN; Eli Lilly; January 2019. Accessed October 2020.

2.     Pemfexy [package insert]. Woodcliff Lake, NJ; Eagle Pharmaceuticals, Inc.; February 2020. Accessed October 2020.

3.     3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for pemetrexed. National Comprehensive Cancer Network, 2020. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed October 2020.

4.     Castagneto B, Botta M, Aitini E, et al, “Phase II Study of Pemetrexed in Combination With Carboplatin in  Patients With Malignant Pleural Mesothelioma (MPM),” Ann Oncol, 2008, 19(2):370-3.

5.     Ceresoli GL, Zucali PA, Favaretto AG, et al, “Phase II Study of Pemetrexed plus Carboplatin in Malignant Pleural Mesothelioma,” J Clin Oncol, 2006, 24(9):1443-8.

6.     Taylor P, Castagneto B, Dark G, et al, “Single-Agent Pemetrexed for Chemonaïve and Pretreated Patients With Malignant Pleural Mesothelioma: Results of an International Expanded Access Program,” J Thorac Oncol, 2008, 3(7):764-71

7.     Ciuleanu T, Brodowicz T, Zielinski C, et al, “Maintenance Pemetrexed Plus Best Supportive Care versus Placebo Plus Best Supportive Care for Non-Small-Cell Lung Cancer: A Randomised, Double-Blind, Phase 3 Study,” Lancet, 2009, 374(9699):1432-40.

8.     Grønberg BH, Bremnes RM, Fløtten O, et al, “Phase III Study by the Norwegian Lung Cancer Study Group: Pemetrexed Plus Carboplatin Compared With Gemcitabine Plus Carboplatin as First-Line Chemotherapy in Advanced Non-Small-Cell Lung Cancer,” J Clin Oncol, 2009, 27(19):3217-24.

9.     Hanna N, Shepherd FA, Fossella FV, et al, “Randomized Phase III Trial of Pemetrexed versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy,” J Clin Oncol, 2004, 22(9):1589-97.

10.  Jassem J, Ramlau R, Santoro A, et al, “Phase III Trial of Pemetrexed Plus Best Supportive Care Compared With Best Supportive Care in Previously Treated Patients With Advanced Malignant Pleural Mesothelioma,” J Clin Oncol, 2008, 26(10):1698-704.

11.  Scagliotti GV, Parikh P, von Pawel J, et al, “Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell Lung Cancer,”J Clin Oncol, 2008, 26(21):3543-51.

12.  Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for  advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508.

13.  Miller DS, Blessing JA, Krasner CN, et al. Phase II Evaluation of Pemetrexed in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian or Primary Peritoneal Carcinoma: A Study of the Gynecologic Oncology Group. J Clin Oncol, 2009, 27(16):2686-91.

14.  Liang Y, Padda SK, Riess JW, et al. Pemetrexed in patients with thymic malignancies previously treated with chemotherapy. Lung Cancer. 2015 Jan;87(1):34-8.

15.  Gbolahan OB, Porter RF, Salter JT, et al. A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma. J Thorac Oncol. 2018 Dec;13(12):1940-1948.

16.  Raizer JJ, Rademaker A, Evens AM, et al. Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma. Cancer. 2012 Aug 1;118(15):3743-8.

17.  Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.

18.  Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue Briefs/Drug_Waste_2019.pdf

19.  Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.

20.  Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078-2092. doi:10.1056/NEJMoa1801005.

21.  Wu YL, Lu S, Cheng Y, et al. Efficacy and safety of pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment in Chinese patients with advanced nonsquamous non-small cell lung cancer. Lung Cancer. 2014;85(3):401-407. doi:10.1016/j.lungcan.2014.07.007.

22.  Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012;13(3):247-255. doi:10.1016/S1470-2045(12)70063-3.

23.  Vogelzang NJ, Rusthoven JJ, Symanowski J, 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(14):2636-2644. doi:10.1200/JCO.2003.11.136.

24.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer Version 1.2020. National Comprehensive Cancer Network, 2020. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed July 2020.

25.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thymomas and Thymic Carcinomas Version 1.2020. National Comprehensive Cancer Network, 2020. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed October 2020.

26.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Malignant Pleural Mesothelioma Version 12.2020. National Comprehensive Cancer Network, 2020. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed October 2020.

27.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers Version 23.2020. National Comprehensive Cancer Network, 2020. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed October 2020.

28.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer Version 68.2020. National Comprehensive Cancer Network, 2020. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed October 2020.

29.  Lexi-Comp Online. (2021). AHFS DI. Pemetrexed. Retrieved January 11, 2021 from Lexi-Comp Online with AHFS.

30.  MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2020, November). Pemetrexed. Retrieved January 11, 2021 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  10/8/2005

MOST RECENT REVIEW DATE:   7/31/2021

ID_MRx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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