CurrentEmblemHealthPolicy Evolent Clinical Guideline 3028 for Zepzelca (lurbinectedin)

Zepzelca (lurbinectedin) coverage and utilization guideline

Defines accepted indications, exclusions, coding, and utilization management requirements for Zepzelca (lurbinectedin) for providers ordering medication under Evolent-managed lines of business; applies to prior authorization and reimbursement decisions.

Policy Summary

PayerEmblemHealth

PolicyZepzelca (lurbinectedin) coverage and utilization guideline

Policy CodePolicy Evolent Clinical Guideline 3028 for Zepzelca (lurbinectedin)

Change TypeRevised template and exclusion updates

Effective Date

Next Review Date

Key ActionSubmit prior authorization with supporting FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template and updated exclusion criteria, replacing prior UM ONC_1408 guideline.

J9223HCPCS code for lurbinectedin (0.1 mg)

6Applicable LOB

NoneContraindications/warnings

Non-pulmonary neuroendocrineExplicit exclusion

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General medical necessity

Coverage is allowed only when supported by one of the following and not excluded by criteria below.

Support requirements: Request is supported by FDA approved product labeling OR CMS-recognized compendia OR NCCN/ASCO clinical guidelines OR acceptable peer-reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements

Per Purpose section; CMS manual Chapter 15 referenced

SCLC (extensive/metastatic) coverage stance

Specific stance for Small Cell Lung Cancer (SCLC):

SCLC restriction: Use for metastatic/extensive-stage SCLC is not supported by Evolent due to lack of confirmatory randomized survival benefit versus standard second-line therapies (e.g., intravenous topotecan or the CAV regimen)

Providers should refer to alternative agents/regimens on Evolent Pathways

second-line

Second-line use note: Evolent does not endorse lurbinectedin as a preferred second-line therapy for extensive-stage SCLC because randomized data demonstrating superior overall survival compared to standard second-line options (e.g., IV topotecan, CAV) are not available

References phase II accelerated-approval basis and lack of confirmatory randomized trials

Use of Zepzelca (lurbinectedin) is excluded for non-pulmonary neuroendocrine carcinomas. Examples include poorly differentiated neuroendocrine carcinoma of the gastrointestinal (GI) tract, genitourinary (GU) sites, head and neck, and metastatic poorly differentiated neuroendocrine carcinoma of unknown primary origin. This exclusion is based on the lack of clinical trial evidence supporting Zepzelca in these non-lung neuroendocrine settings.

Evolent does not support use of Zepzelca (lurbinectedin) for metastatic/extensive-stage Small Cell Lung Cancer (SCLC). The FDA approval was an accelerated approval based on a phase II basket trial that used surrogate endpoints (overall response rate), and there are no confirmatory randomized data demonstrating a survival benefit versus standard second-line therapies (for example, intravenous topotecan or the CAV regimen). Providers should refer to alternative agents and regimens recommended by Evolent Pathways.

Provider Actions and Utilization Management

Prior Authorization

Prior Authorization Required

Prior authorization is required for all requests for Zepzelca (lurbinectedin) and will be processed by Evolent. Medications not authorized by Evolent may be deemed not approvable and therefore not reimbursable. Continuation prior authorization may be allowed when the member has not experienced disease progression on the requested medication, the medication was used within the last year without a lapse of more than 30 days of having an active authorization, and no additional medications are being added to the continuation request.

All initial and continuation requests must be submitted to Evolent for review.
Continuation requests are exempt from re‑review only if all continuation conditions are met (no disease progression; used within last year without >30 day lapse; no new meds added).

Step Therapy

Step Therapy / Preferred Alternatives

Use of Zepzelca (lurbinectedin) for metastatic/extensive‑stage small cell lung cancer (SCLC) is not supported by Evolent. Alternative, guideline‑supported second‑line regimens (for example, intravenous topotecan or CAV) should be considered; see Evolent Pathways for recommended alternatives.

Zepzelca accelerated FDA approval was based on a phase II trial using surrogate endpoints; no confirmatory randomized data show superior survival vs standard‑of‑care second‑line options.
Evolent does not support Zepzelca for metastatic/extensive‑stage SCLC; refer to alternative agents/regimens in Evolent Pathways.

Documentation Required

Required Supporting Documentation

Provider must support the medication request with one or more of the following: FDA‑approved product labeling, CMS‑recognized compendia, NCCN or ASCO clinical guidelines, or acceptable peer‑reviewed literature that meets CMS standards (see Medicare Benefit Policy Manual Chapter 15). The submitted evidence should adequately represent the patient and disease characteristics, the administered regimen, and clinically meaningful outcomes.

Acceptable evidence sources: FDA labeling, CMS‑recognized compendia, NCCN, ASCO, or peer‑reviewed literature meeting CMS criteria.
Peer‑reviewed evidence should address representativeness of the population, regimen, and clinically meaningful outcomes (e.g., ASCO‑recommended thresholds).

Denial Risk

Denial Triggers

Requests may be denied if the requested use is not supported by FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidelines, or sufficient peer‑reviewed evidence. Denial triggers include investigational or off‑label indications lacking adequate evidence, use in excluded diagnoses (for example non‑pulmonary poorly differentiated neuroendocrine carcinomas), dosing that exceeds the single‑dose limit (3.2 mg/m2), or investigational combinations/indications not generally accepted by the medical community.

Excluded indications: neuroendocrine carcinoma of non‑lung origin (GI, GU, head & neck, unknown primary).
Dose exceedance: single dose > 3.2 mg/m2.
Insufficient evidence: off‑label or investigational uses not supported by CMS compendia or acceptable peer‑reviewed literature may be denied.

Regimen	Indication	Coverage stance / notes
Lurbinectedin (with or without doxorubicin)	Second-line therapy for extensive-stage (metastatic) Small Cell Lung Cancer (SCLC)	not_covered — Use for metastatic/extensive-stage SCLC is not supported by Evolent due to lack of confirmatory randomized survival benefit versus standard second-line therapies; providers should refer to alternative agents/regimens (e.g., IV topotecan, CAV) on Evolent Pathways.

Definitions

Extensive-stage Small Cell Lung Cancer (SCLC) — definition & policy stance

DefinitionExtensive-stage (metastatic) Small Cell Lung Cancer (SCLC): disease stage for which randomized data supporting lurbinectedin superiority over standard second-line therapies are lacking per Evolent review

Coverage stanceUse of Zepzelca (lurbinectedin) is not supported by Evolent for treatment of metastatic/extensive-stage SCLC due to lack of confirmatory randomized survival benefit versus standard second-line options (e.g., IV topotecan, CAV)

Evidence rationaleFDA approval was accelerated based on a phase II basket trial using surrogate endpoints (overall response rate); no confirmatory randomized trials show superior overall survival

Alternative recommendationsProviders should refer to alternative agents/regimens recommended by Evolent Pathways (e.g., IV topotecan, CAV)

OpenPayer

Zepzelca (lurbinectedin) coverage and utilization guideline

Coverage Criteria for Zepzelca (lurbinectedin)

Coding and Dose Limits

Provider Actions and Utilization Management

Regimens and Therapeutic Recommendations

Definitions

Background and Regulatory Context