Lutetium Therapeutic Radiopharmaceuticals Form

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Lutetium Therapeutic Radiopharmaceuticals - Medical Policy
Updated Revision Effective: February 1, 2025 Policy Number:

UM700POL

Approval Date: 12/19/2024

Line(s) of Business:

FF
SF
Medicare
MedSupp-G
MedSupp-I
Medicaid

Description

Radiopharmaceuticals, also known as radionuclides, are composed of a radioisotope coupled to an organic molecule and are used for diagnostic and therapeutic purposes. The organic molecule targets the radioisotope to specific organs, tissues, or cells. Examples of radionuclides include peptide receptor radioligand therapy and metaiodobenzylguanidine (MIBG).

The peptide receptor radioligand therapy lutetium 177 (Lu 177) dotatate (Lutathera®) is a radiolabeled- somatostatin analog indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults.

Gastroenteropancreatic Neuroendocrine Tumors Neuroendocrine cells are widely distributed throughout the body, and tumors arising from these cells can occur in most organs. In the digestive system, including the tubular gastrointestinal tract and the pancreas, neuroendocrine tumors are generally divided into two major categories, well-differentiated neuroendocrine tumors (NETs) and poorly differentiated (high-grade) neuroendocrine carcinomas. These two major categories of neuroendocrine tumors behave differently in terms of biologic aggressiveness and in approach to treatment.

Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which have been referred to as carcinoid tumors or pancreatic islet cell tumors, are generally indolent, but all are potentially malignant, and the clinical course may be highly variable. Symptomatic disease may be due to either tumor bulk, including pain and/or bowel obstruction, or due to secretion of serotonin and other vasoactive substances, sometimes referred to as carcinoid syndrome.

The general treatment approach to well-differentiated GEP-NETs involves resecting potentially resectable disease, including metastasectomy. Unresectable, asymptomatic disease may involve observation, especially if tumor burden is limited, or initial therapy with a somatostatin analog if tumor burden is high. Unresectable, symptomatic disease usually involves initial therapy with a somatostatin analog (e.g. octreotide), and dose escalation as needed for control of symptoms of carcinoid syndrome and control of tumor growth. Patients with radiologic or symptom progression despite somatostatin analog therapy may benefit from noncurative debulking therapy or nonsurgical

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liver-directed therapy. Patients with more widespread disease that is not eligible for liver-directed therapy may benefit from systemic treatment with molecularly targeted agents, such as everolimus.

Lutetium 177 (Lu 177) dotatate (Lutathera®) is a targeted form of systemic radiotherapy that binds to cell surface somatostatin receptors, and once internalized, induces cellular damage by free radical formation. Most GEP-NETs express high-affinity receptors for somatostatin, and somatostatin-based imaging can provide information on tumor burden and location. Lutetium 177 (Lu 177) dotatate has been proposed as a treatment option in patients with GEP-NETs who progress despite first-line therapy.

Prostate-specific Membrane Antigen (PSMA)-positive Metastatic Castration-resistant Prostate Cancer Metastatic castration-resistant prostate cancer remains clinically challenging despite multiple drug classes that delay progression of disease. Prostate-specific membrane antigen (PMSA) is expressed in metastatic castration-resistant prostate cancer. Radioligand therapies such as Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto) can selectively target prostate cancer cells in patients who have a PSMA-positive gallium-68- labeled PSMA-11 positron-emission tomographic-computed tomographic scan.

 Line of Business

Commercial:
•

Refer to criteria under the Policy section in this medical policy.

Medicaid – BeHealthy:

• Refer to criteria under the Policy section in this medical policy.
• There are no MassHealth guidelines for Lutetium Therapeutic Radiopharmaceuticals.

Medicare:

• Health New England follows Local Coverage Determination (LCD) Chemotherapy Drugs and their Adjuncts (L37205) for Lutetium 177 (Lu 177) vipivotide tetraxetan, which is a National Comprehensive Cancer Network (NCCN) category 1 treatment. https://www.cms.gov/medicare-coverage- database/search.aspx

Policy

Lutetium 177 (Lu 177) dotatate (Lutathera)

I. Lutetium 177 (Lu 177) dotatate is considered MEDICALLY NECESSARY for the treatment of adult patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) or bronchopulmonary or thymus neuroendrocrine tumors when the following criteria are met:

1. Member has unresectable, locally advanced or metastatic disease; AND
2. Member has had disease progression despite somatostatin analog therapy or molecularly targeted therapy (e.g. everolimus); AND
3. An appropriate imaging study has been performed to document over-expression of somatostatin receptors by the target lesions; AND
4. The tumor is well differentiated with a Ki-67 index of 20% or less.

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II. Lutetium 177 (Lu 177) dotatate is considered EXPERIMENTAL and INVESTIGATIONAL when the above criteria are not met, treatment is greater than the Food and Drug Administration (FDA) approved regimen or the treatment is for non-FDA approved indications such as pheochromocytomas and paragangliomas.

Lutetium 177 (Lu 177) vipivotide tetraxetan (Pluvicto)

I. Lutetium 177 (Lu 177) vipivotide tetraxetan is considered medically necessary for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer when the following criteria are met:

1. Member has unresectable metastatic disease; AND
2. Member had a PSMA-positive gallium-68-labeled PSMA-11 positron-emission tomographic-computed tomographic scan; AND
3. The patient has disease progression despite advanced androgen therapy, e.g., at least one androgen- receptor-pathway inhibitor, as demonstrated by prostate specific antigen (PSA) progression after at least four weeks; AND

4. The patient has disease progression after at least one taxane regimen.

   II. Lutetium 177 (Lu 177) vipivotide tetraxetan is considered EXPERIMENTAL and INVESTIGATIONAL when the above criteria are met, treatment is greater than the Food and Drug Administration (FDA) approved regimen or the treatment is for non-FDA approved indications.

   Policy Guidelines and Definitions

   Definitions:

   PSMA (prostate-specific membrane antigen): A protein found mainly on prostate cancer cells. Also known as folate hydrolase I and glutamate carboxypeptidase II.

   mCRPC: Metastatic castration-resistant prostate cancer.

   Somatostatin Receptor (+): A protein on the surface of cells that binds to a hormone called somatostatin, which helps control other hormones in the body. Somatostatin receptors are found on many different types of cells, and they may be found in higher-than-normal amounts on some types of cancer cells. Knowing the amount of somatostatin receptor in tumor tissue may help diagnose cancer and plan treatment. NCI (National Cancer Institute) dictionary.

   Neuroendocrine Tumors (NETs): A tumor that forms from cells that release hormones into the blood in response to a signal from the nervous system. Neuroendocrine tumors may make higher-than-normal amounts of hormones, which can cause many different symptoms. These tumors may be benign (not cancer) or malignant (cancer). Some examples of neuroendocrine tumors are carcinoid tumors, islet cell tumors, medullary thyroid cancer, pheochromocytomas, neuroendocrine carcinoma of the skin (Merkel cell cancer), small cell lung cancer, and large cell neuroendocrine carcinoma (a rare type of lung cancer). NCI (National Cancer Institute) dictionary.

   Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): Rare tumors that can form in the pancreas or GI tract including stomach, appendix, small intestine, rectum or colon. These tumors usually form in hormone-

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secreting cells. The tumors may be malignant or benign. Tumors may secrete extra amounts of hormones or other substances that may cause symptoms of a disease (i.e., carcinoid syndrome).

Carcinoid Syndrome: Combination of symptoms due to the release of serotonin and other substances from carcinoid tumors of the GI tract. Symptoms may include: facial flushing, diarrhea, bronchial spasms, rapid heart rate, and sudden drops in blood pressure or flat angiomas (small blood collections of dilated blood vessels) of the skin.

Carcinoid tumor: Slow growing tumor generally in small intestine and rectum. These tumors may spread to the liver or other sites within the body. These tumors may secrete serotonin or prostaglandins which results in carcinoid syndrome.

Pheochromocytoma: Rare tumor of adrenal gland tissue. Tumor releases too much epinephrine and norepinephrine. These two hormones control the heart rate, blood pressure and metabolism.

Peptide Receptor Radionuclide Therapy (PRRT): A type of radiation therapy used to treat certain types of neuroendocrine tumors. A radioactive chemical is linked to a peptide (small protein) that targets cancer cells. When this radioactive peptide is injected into the body, it binds to a specific receptor found on some cancer cells.
The radioactive peptide builds up in these cells and helps kill the cancer cells without harming normal cells.
Peptide receptor radionuclide therapy is a type of targeted therapy. Also called PRRT. NCI (National Cancer Institute) dictionary.

Foregut Neuroendocrine Tumors: Tumors that arise in the esophagus, stomach, pancreas and duodenum

Midgut Neuroendocrine Tumors: Tumors that arise in the jejunum and the proximal colon

Hindgut Neuroendocrine Tumors: Tumors that arise from 1/3 of the transverse colon, descending colon, sigmoid colon, rectum and upper anal canal.

Definitions for NCCN Categories: The specific definitions of the NCCN categories for recommendations are the following: • Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate; • Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate; • Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate; • Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. Well-differentiated neuroendocrine tumors: Include low-grade (G1) and intermediate-grade (G2) tumors, which correlate with a defined Ki-67 proliferation index, as determined by an immunohistochemical stain. Well- differentiated, low grade neuroendocrine tumors have a Ki-67 index of <3%, and well-differentiated, intermediate-grade neuroendocrine tumors have a Ki-67 index of 3-20%.

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Coding Guidance

Code
Description
PA HCPCS

A9513 Lutetium Lu 177, dotatate, therapeutic, 1 mCi

Yes A9607 Lutetium LU 177 Vipivotide Tetraxetan, therapeutic, 1 Millicurie Yes

CPT® Copyright 2025 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

Note: CPT/HCPCS codes are included for informational purposes and may not be all-inclusive. Inclusion or exclusion of a CPT/HCPCS code(s) does not signify or imply that the service described by the code is a covered or non-covered health service. Benefit coverage for health services is determined by the member’s specific benefit plan document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to reimbursement or guarantee of payment. Other policies and coverage determination guidelines may apply.

References

U.S. Food and Drug Administration (FDA). Lutathera (lutetium Lu 177 dotatate). Highlights of prescribing information. January 2018.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208700s000lbl.pdf.

U.S. Food and Drug Administration. FDA approves new treatment for certain digestive tract cancers. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm594043.htm.

Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. PMID: 28076709.
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1607427.

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Neuroendocrine and Adrenal Tumors, version 1.2018.
https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf.

Brabander T, van der Zwan W, Teunissen J, et al. Long-term efficacy, survival, and safety of [177LuDOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res. 2017 Aug 15;23(16):4617-4624. PMID: 28428192. https://www.ncbi.nlm.nih.gov/pubmed/28428192.

Lutathera Lu 177 Dotatate (Lutathera, Advanced Accelerator Applications USA Inc.) for the treatment of Gastroenteropancreatic Neuroendocrine Tumors (2019, Sept. 5).
https://www.hayesinc.com/publications/precision-medicine/precision-therapy-assessment/lutetium-lu-177- dotatate-lutathera-advanced-accelerator-applications-usa-inc-for-the-treatment-of-gastroenteropancreatic- neuroendocrine-tumors/pta-lutathera4653/

Neuroendocrine tumors (March 14, 2020).

https://www.mayoclinic.org/diseases-conditions/neuroendocrine-tumors/symptoms-causes/syc-20354132

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Mechanism of Action, About Pluvicto, (2022).

Mechanism of Action I PLUVICTO (novartis.com)

FDA D.I.S.C.O.: Burst Edition: FDA approval of Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval- pluvicto-lutetium-lu-177-vipivotide-tetraxetan-treatment- adult#:~:text=On%20March%2023%2C%202022%2C%20the,pathway%20inhibition%20and%20taxane%2Dbased

Lowrance, W., Breau, R., Chou, R., Chapin, B.F., Crispino, T., Dreicer, R., Jarrard, D.F., Kibel, A.S., Morgan, T. M., Morgans, A.K., OH, W.<., Resnick, M.R., Zietman, A., Cookson, M.S. (2020). Advanced prostate cancer: AUA/ASTRO/SUO guideline. 2020 by the American Urological Association. https://www.auanet.org/guidelines/oncology-guidelines

Novartis. Learn about PLUVICTO (Lutetium Lu 177 vipivotide tetraxetan). https://www.hcp.novartis.com/products/pluvicto/psma-positive-mcrpc/

Keam, S, Lutetium Lu 177 Vipivotide Tetraxetan: First Approval (May 13, 2022). from:

https://doi.org/10.1007%2Fs40291-022-00594-2

Policy Implementation

Approved by the Medical and Pharmacy Policy Committee

Kate McIntosh MD MBA

Chief Medical Officer

Saad Usmani MD MBA

Medical Director

Date Update 11/2019 Initial policy effective date 12/2023 • Title changed from Lutetium Lu 177 Dotatate, Therapeutic (Lutathera) and
Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto) . • Minor criteria changes for Commercial and Medicaid. • LCD added for Medicare. • References updated. 12/2024 Reviewed with no criteria changes.

Medical Criteria Disclaimer

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Property of Health New England. All rights reserved. The treating physician or primary care provider must submit to Health New England the clinical evidence that the patient meets the criteria for the treatment, testing or surgical procedure. Without this documentation and information, Health New England will not be able to properly review the request for prior authorization. The clinical review criteria reflect how Health New England determines whether certain services or supplies are medically necessary. Health New England established the clinical review criteria based upon a review of currently available clinical information (including clinical outcome studies in the peer-reviewed published medical literature, regulatory status of the technology, evidence-based guidelines of public health and health research agencies, evidence-based guidelines and positions of leading national health professional organizations, views of physicians practicing in relevant clinical areas, and other relevant factors).
Health New England expressly reserves the right to revise these conclusions as clinical information changes, and welcomes further relevant information. Each benefit program defines which services are covered. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered and/or paid for by Health New England, as some programs exclude coverage for services or supplies that Health New England considers medically necessary. If there is a discrepancy between this guideline and a member's benefits program, the benefits program will govern. In addition, coverage may be mandated by applicable legal requirements of a state, the Federal Government or the Centers for Medicare & Medicaid Services (CMS) for Medicare and Medicaid members. All coding and web site links are accurate at time of publication. Health New England has adopted the herein policy in providing management, administrative and other services to its Health Plan.