CurrentNeighborhood Health Plan of Rhode IslandPolicy UM ONC_1041

Luteinizing Hormone Releasing Hormone (LHRH) Agonists and Antagonists

Defines accepted indications, continuation criteria, exclusions, dosing limits, and evidence standards for coverage of LHRH agonists and antagonists (e.g., leuprolide, goserelin, triptorelin, degarelix, relugolix) for cancer treatment, fertility preservation, and related uses. Applies to medication requests processed by Evolent/UM for Neighborhood Health Plan of Rhode Island members.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyLuteinizing Hormone Releasing Hormone (LHRH) Agonists and Antagonists

Policy CodePolicy UM ONC_1041

Change TypeNo material change

Effective DateJul 26, 2024

Next Review Date

Key ActionAll medication requests for LHRH agents must be processed/authorized by Evolent Utilization Management; medications not authorized may be not approvable and not reimbursable

POLICY UPDATE CHANGES

No material clinical or coverage changes in this update.

3Covered Indications (Breast, Prostate, Fertility preservation)

6Named Drugs Listed

1Prior Authorization Required (Evolent UM)

multipleCommittee Review Dates (2011-2024)

This policy (UM ONC_1041) concerns Luteinizing Hormone Releasing Hormone (LHRH) Agonists and Antagonists and the conditions under which they are covered with criteria for cancer treatment and fertility preservation (named products include leuprolide acetate/mesylate, triptorelin, goserelin, degarelix, and relugolix). Evolent Utilization Management processes medication requests and enforces prior authorization, coverage, and dosing limits; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Effective date: 2024-07-26; Committee approval / last review / approval date: July 10, 2024.

Key thresholds and quick facts

Lupron Depot/Eligard single dose limitsLeuprolide acetate IM Depot 45 mg every 6 months; Lutrate Depot 22.5 mg every 3 months

Camcevi single dose limitLeuprolide mesylate 42 mg every 6 months

Zoladex single dose limitGoserelin 10.8 mg every 3 months

Trelstar single dose limitTriptorelin 22.5 mg every 6 months

Firmagon dosing limitsDegarelix 240 mg (loading) or 80 mg monthly (continuation)

Orgovyx dosing limitsRelugolix 360 mg (loading) or 120 mg (continuation); max 30 (120 mg) tablets per month

Named drugs listed6 (Eligard/Lupron/Lutrate, Camcevi, Trelstar, Zoladex, Firmagon, Orgovyx)

Covered indications count3 (Breast, Prostate, Fertility preservation)

Prior authorization requiredEvolent UM processes medication requests (Prior authorization required)

Committee review datesMultiple dates 01/12/11 through 08/09/23; approval date July 10, 2024; effective July 26, 2024

Medical Necessity Criteria

General requirements and evidence standard

Use must be supported by one of the following sources and medication requests are processed by Evolent:

ALL of the following

Supportive evidence: Use must be supported by FDA approved product labeling OR CMS‑approved compendia OR NCCN OR ASCO clinical guidelines OR peer‑reviewed literature that meets the requirements of the CMS Medicare Benefit Policy Manual Chapter 15
Reference: Medicare Benefit Policy Manual Chapter 15 standards; see policy references for acceptable sources
Evolent processing: Medication requests are processed by Evolent; medications not authorized by Evolent may be deemed not approvable and not reimbursable
Evolent UM is responsible for processing and authorization

Continuation requests exemption

Continuation requests for a not-approvable medication are exempt if ALL of the following are met:

Continuation request exemption: Requested medication was used within the last year

Part of the three‑point continuation exemption

Continuation request exemption: Member has not experienced disease progression and/or no intolerance to the requested medication

Part of the three‑point continuation exemption

Continuation request exemption: Additional medication(s) are not being added to the continuation request

Part of the three‑point continuation exemption

Breast cancer indication

Covered when ALL of the following are met:

Breast cancer indications: Use of LHRH Agonists (leuprolide acetate, goserelin, or triptorelin) in combination with endocrine therapy (e.g., tamoxifen, aromatase inhibitors) for ovarian suppression in premenopausal women

Applies to ovarian suppression and adjuvant/recurrent/metastatic use

Breast cancer indications: Use of LHRH Agonists in men with ER/PR positive breast cancer as adjuvant therapy or for recurrent/metastatic disease

Male breast cancer, ER/PR positive

Fertility preservation in women undergoing cytotoxic chemotherapy

Covered when ALL of the following are met:

Fertility preservation: Use of LHRH Agonists (leuprolide acetate, goserelin, or triptorelin) in conjunction with fertility preservation methods for women undergoing cytotoxic chemotherapy

See ASCO fertility guidelines and referenced trials for supporting evidence

Prostate cancer indication

Covered when ANY of the following clinical contexts apply:

Prostate cancer indications: Use of LHRH Agonists or Antagonists (leuprolide acetate/mesylate, goserelin, triptorelin, degarelix, or relugolix) as single agent for castrate sensitive or castrate resistant M0 or M1 prostate cancer

Single‑agent use for castrate sensitive or resistant disease

Prostate cancer indications: Use of LHRH Agonists or Antagonists in combination with an antiandrogen with or without chemotherapy for castrate sensitive or castrate resistant M0 or M1 prostate cancer

Combination therapy context

Investigational and Off‑Label Exclusions

Off-label or investigational uses may be excluded when they lack sufficient supporting evidence or are not generally accepted by the medical community. The policy requires that use be supported by one of the following: FDA product labeling, CMS‑approved compendia, NCCN, ASCO clinical guidelines, or peer‑reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 standards.

The policy explicitly states that off‑label indications that are not supported by adequate evidence may be considered investigational and excluded; the document defines criteria for sufficient evidence including representation of the patient/cancer population, representation of concomitant therapies, clinically meaningful outcomes (ASCO-recommended thresholds such as HR < 0.80 and at least 3 months survival benefit for OS/PFS), appropriate study design, allowance for non-randomized trials with sufficient subjects, and that case reports or abstracts without full peer‑reviewed articles generally do not provide adequate evidence.

Exclusions, evidence standards, and Evolent processing

Focused exclusion/evidence processing criteria from general requirements (acceptable evidence and Evolent processing):

Evidence standard - acceptable sources: Support by FDA approved product labeling OR CMS‑approved compendia OR NCCN OR ASCO clinical guidelines OR peer‑reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements

Defined in policy purpose and references

Investigational/off‑label exclusion: Off‑label indications lacking sufficient evidence or not accepted by the medical community may be considered investigational and excluded from coverage

Sufficient evidence is further defined by study population representation, regimen representation, clinically meaningful outcomes, study design, and acceptable trial types

Evolent processing and authorization: Medication requests are processed by Evolent; medications not authorized by Evolent may be deemed not approvable and not reimbursable

Evolent UM processes all medication requests per policy purpose

Provider Actions & Administrative Requirements

Prior Authorization

Medication requests processed by Evolent

All medication requests for LHRH agonists and antagonists must be processed and authorized by Evolent Utilization Management. Medications that are not authorized by Evolent may be deemed not approvable and therefore not reimbursable.

Eligard/Lupron/Lutrate (leuprolide acetate)
Camcevi (leuprolide mesylate)
Trelstar (triptorelin acetate)
Zoladex (goserelin acetate)
Firmagon (degarelix)
Orgovyx (relugolix)

Documentation Required

Supportive evidence requirement

Use must be supported by one of the following sources: FDA approved product labeling, CMS‑approved compendia, National Comprehensive Cancer Network (NCCN) guidelines, American Society of Clinical Oncology (ASCO) clinical guidelines, or peer‑reviewed literature that meets the standards in the CMS Medicare Benefit Policy Manual Chapter 15.

Denial Risk

Investigational/off‑label use exclusion

Off‑label or investigational uses that lack sufficient supporting evidence or are not generally accepted by the medical community may be considered investigational and excluded from coverage.

Billing Rule

Dosing limits enforcement

Claims that exceed specified single‑dose limits or the monthly tablet maximum for named products may be excluded or denied per the policy dosing limits.

Leuprolide acetate IM Depot: 45 mg every 6 months; Lutrate Depot 22.5 mg every 3 months
Leuprolide mesylate (Camcevi) 42 mg every 6 months
Goserelin (Zoladex) 10.8 mg every 3 months
Triptorelin (Trelstar) 22.5 mg every 6 months
Degarelix (Firmagon): 240 mg loading dose; 80 mg monthly continuation
Relugolix (Orgovyx): 360 mg loading dose; 120 mg continuation; maximum 30 (120 mg) tablets per month

Background & Supporting Evidence

Purpose: to define accepted indications for LHRH agonists/antagonists in cancer care (including FDA‑approved and selected off‑label uses) and fertility preservation, and to describe the evidence standard and authorization processes. Evolent UM is responsible for processing all medication requests; medications must be authorized by Evolent to be approvable and reimbursable.

Scope: applies to named LHRH products (e.g., leuprolide acetate/mesylate, triptorelin, goserelin, degarelix, relugolix) and covers specified indications including breast cancer (ovarian suppression/adjuvant or recurrent/metastatic ER/PR+ disease), fertility preservation in women undergoing cytotoxic chemotherapy, and prostate cancer (castrate sensitive or castrate resistant M0/M1) as single agent or in combination. The policy establishes continuation exemptions, dosing limits, and documentation/evidence requirements used by Evolent UM when adjudicating requests.

Study/Guideline	Reference
HERO trial (relugolix)	Shore et al, N Engl J Med 2020;382:2187-2196
ASCO fertility guidelines	Loren AW et al., J Clin Oncol. 2013
POEMS/S0230 (goserelin)	Moore HC et al., N Engl J Med. 2015

Definitions

Definitions (operational terms used in criteria). See also the Continuation request exemption definition.

Continuation request exemption (definition): Continuation requests for previously used, not‑approvable medications within last year with no progression/intolerance and no additional meds are exempt from policy requirements

Links to the Continuation requests exemption criteria

Sufficient evidence (definition): Evidence supported by CMS compendia or acceptable peer‑reviewed literature as defined by criteria in Exclusion section (study representation, outcomes, design, etc.)

See Exclusion criteria III.C and III.C.1-7 for operational elements of sufficient evidence

OpenPayer

Luteinizing Hormone Releasing Hormone (LHRH) Agonists and Antagonists

Coverage Summary

Medical Necessity Criteria

Investigational and Off‑Label Exclusions

Coding (Named drugs)

Provider Actions & Administrative Requirements

Background & Supporting Evidence

Revision History

leuprolide acetate	Eligard/Lupron/Lutrate Depot (leuprolide acetate)
leuprolide mesylate	Camcevi SC Depot (leuprolide mesylate)
triptorelin acetate	Trelstar (triptorelin acetate)
goserelin acetate	Zoladex (goserelin acetate)
degarelix	Firmagon (degarelix)
relugolix	Orgovyx (relugolix)