CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Zepzelca (lurbinectedin) coverage and utilization guideline

Defines accepted indications, exclusions, coding, and evidence requirements for coverage of Zepzelca (lurbinectedin) for members served by Evolent on behalf of Neighborhood Health Plan of Rhode Island.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyZepzelca (lurbinectedin) coverage and utilization guideline

Policy CodePolicy N/A

Change TypeExclusion criteria updatedtemplate conversion

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and support therapy with FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template and replaced prior UM ONC_1408 Zepzelca (lurbinectedin) guideline.

Updated exclusion criteria.

J9223HCPCS code listed for lurbinectedin

noneContraindications/Warnings

multipleApplicable lines of business

non-pulmonary PD NECExplicit exclusion example

Coverage Criteria for Zepzelca (lurbinectedin)

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General coverage and exclusion criteria

Covered when supported by one of the following sources and not excluded by criteria below

Support requirements: Therapy must be supported by FDA approved product labeling OR CMS-recognized compendia OR NCCN or ASCO clinical guidelines OR peer-reviewed literature meeting CMS standards

See chunk 0 for list of acceptable evidence

Exclusions: Not supported for metastatic/extensive-stage Small Cell Lung Cancer (SCLC); excluded: non-pulmonary poorly differentiated neuroendocrine carcinoma (e.g., GI, GU, head and neck, unknown primary); dosing exceeding single dose limit of 3.2 mg/m2; investigational/off-label uses lacking sufficient evidence or CMS-recognized compendium/supporting peer-reviewed literature

See chunks 2 and 4

The policy explicitly excludes Zepzelca (lurbinectedin) for use in non-pulmonary poorly differentiated neuroendocrine carcinomas — for example, poorly differentiated neuroendocrine carcinoma of the gastrointestinal tract, genitourinary tract, head and neck, and metastatic poorly differentiated neuroendocrine carcinoma of unknown primary origin — due to lack of clinical trial evidence in these settings. Additionally, any dosing that exceeds a single dose of 3.2 mg/m2 is exclusionary. The guideline also excludes investigational or off-label uses that do not meet standards for sufficient evidence (e.g., not supported by CMS-recognized compendia or acceptable peer-reviewed literature), and notes that abstracts without full peer‑reviewed articles are not acceptable evidence for coverage.

Zepzelca (lurbinectedin) is not supported by this policy for treatment of metastatic/extensive-stage small cell lung cancer (SCLC). The policy rationale is that the drug’s FDA approval was accelerated on the basis of a phase II single-arm (basket) trial using surrogate endpoints such as overall response rate, and there are no confirmatory randomized data demonstrating superior survival compared with standard second-line options (for example, intravenous topotecan or the CAV regimen). Requests for SCLC use therefore may be denied when adequate randomized evidence of clinical benefit is lacking.

Covered Regimens and Alternatives

Regimen	Indication / Line of therapy	Coverage stance	Rationale / Notes
Zepzelca (lurbinectedin) monotherapy	Second-line therapy for extensive-stage / metastatic small cell lung cancer (SCLC)	Not Covered	Use is not supported by this guideline because FDA accelerated approval was based on a single‑arm phase II trial using surrogate endpoints (overall response rate); no confirmatory randomized data demonstrate superior survival compared with standard second‑line options such as intravenous topotecan or the CAV regimen. Providers should refer to alternative agents/regimens on Evolent Pathways.

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior authorization required; continuation exemptions and timing

Prior authorization is required for Zepzelca (J9223). Continuation (renewal) requests may be exempt from prior authorization only if the member has not experienced disease progression on the 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.

Prior authorization required for J9223 (lurbinectedin).
Continuation exempt only if: no disease progression; prior use within last year without >30-day lapse; no additional meds added.

Step Therapy

Refer to Evolent Pathways for preferred second-line alternatives

Evolent refers providers to alternative agents and regimens recommended on Evolent Pathways for second-line therapy in extensive-stage/metastatic small cell lung cancer instead of Zepzelca.

See Evolent Pathways for recommended second-line alternatives (e.g., intravenous topotecan or the CAV regimen).

Documentation Required

Supporting documentation and acceptable evidence

Treatment requests must be supported by one of the following evidence sources: FDA product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or peer-reviewed literature that meets CMS standards; abstracts without full articles are not acceptable and off‑label uses require sufficient supporting evidence per the policy's criteria.

Acceptable support: FDA labeling; CMS-recognized compendia; NCCN or ASCO guidelines; peer‑reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 standards.
Not acceptable: meeting abstracts without full published articles.
Off‑label/investigational uses must meet the policy's sufficiency criteria (representation of clinical characteristics, regimen, clinically meaningful outcomes, and appropriate study design).

Denial Risk

Denial triggers: metastatic/extensive SCLC, insufficient evidence, dosing over 3.2 mg/m2

Requests for Zepzelca for metastatic/extensive-stage small cell lung cancer are not supported by this guideline and may be denied; investigational or off‑label uses lacking CMS-recognized compendia or acceptable peer‑reviewed evidence, and dosing that exceeds the single‑dose limit of 3.2 mg/m2, are exclusionary and may be denied.

Use for metastatic/extensive-stage SCLC is not supported by Evolent (no confirmatory randomized survival benefit shown).
Investigational/off-label indications without sufficient evidence or without CMS-recognized compendia support may be denied.
Dosing above the single dose limit of 3.2 mg/m2 is exclusionary.

Definitions and Regulatory Status

Accelerated approval — policy definition and implications

DefinitionFDA accelerated approval granted based on phase II single‑arm data using surrogate endpoints (overall response rate)

LimitationNo confirmatory randomized data demonstrating superior survival versus standard second‑line therapies (e.g., IV topotecan or CAV)

Regulatory contextAccelerated approval requires confirmatory evidence; subsequent phase 3 data (ATLANTIS) failed to show superiority

Coverage implicationUse for metastatic/extensive‑stage SCLC is not supported by this guideline due to lack of confirmatory randomized survival benefit