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| Lurbinectedin (e.g., Zepzelca) | |
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| Description: |
Lurbinectedin (e.g., Zepzelca) is a selective inhibitor of oncogenic transcription. It is an alkylating drug that binds guanines located in the DNA gene promoter area. This binding creates an adduct formation that triggers a cascade of events leading to perturbation of the cell cycle and eventual cell death.
Regulatory Status
Lurbinectedin (e.g., Zepzelca) was approved by the U.S. Food and Drug Administration (FDA) on June 15, 2020 for the treatment of adult individuals with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Lurbinectedin is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). (Zepzelca, 2023).
On October 2, 2025, the Food and Drug Administration approved atezolizumab (e.g., Tecentriq) and lurbinectedin (e.g., Zepzelca) combination as a first-line maintenance therapy for extensive-stage small cell lung cancer.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.
Effective July 1, 2023, prior approval is required for Lurbinectedin
(e.g., Zepzelca).
INITIAL AND CONTINUATION APPROVAL will be for duration of the treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
Effective March 16, 2026
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
Lurbinectedin (e.g., Zepzelca) meets member benefit
Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts
without Primary Coverage Criteria, is considered Medically Necessary and is covered, when ALL the following criteria are met:
METASTATIC SMALL CELL LUNG CANCER
INITIAL APPROVAL:
CONTINUATION OF THERAPY:
EXTENSIVE-STAGE SMALL CELL LUNG CANCER
INITIAL APPROVAL:
CONTINUATION OF THERAPY:
The use of this drug is covered if an FDA-approved oncologic indication exists [not listed as an indication above with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”)]. The use of this drug for off-label indications not listed above is subject to policy 2000030.
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
Lurbinectedin (e.g., Zepzelca) for any indication or circumstance not described above, does not meet member benefit certificate
Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered.
For members with contracts without Primary Coverage Criteria, Lurbinectedin (e.g., Zepzelca) for any indication or circumstance not described above, is considered
not Medically Necessary or is investigational and is not covered.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
POLICY GUIDELINES
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
DOSAGE AND ADMINISTRATION
For FDA labeled indications,
Lurbinectedin (e.g., Zepzelca) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified below.
The recommended dose of Lurbinectedin (e.g., Zepzelca) is 3.2 mg/square meters by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Lurbinectedin (e.g., Zepzelca) is available as a 4mg single dose vial for reconstitution.
Lurbinectedin (e.g., Zepzelca) should be administered as an intravenous infusion by a healthcare professional.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Effective January 2025 to March 15, 2026
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
Lurbinectedin (e.g., Zepzelca) meets member benefit primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 1 year:
Policy Guidelines
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
The use of this drug is covered if an FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
Dosing per FDA Guidelines
The recommended dose of Lurbinectedin (e.g., Zepzelca) is 3.2 mg/square meters by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Lurbinectedin (e.g., Zepzelca) is available as a 4mg single dose vial for reconstitution.
Lurbinectedin (e.g., Zepzelca) should be administered as an intravenous infusion by a healthcare professional.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Lurbinectedin (e.g., Zepzelca) for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the use of Lurbinectedin (e.g., Zepzelca) in any indication or circumstance not described above is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective September 1, 2023 to December 2024
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
Lurbinectedin meets member benefit primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for adult individuals with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy (FDA Zepzelca, 2020) when ALL the following criteria are met:
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 1 year:
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
The use of this drug is covered if an FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
Dosing per FDA Guidelines
The recommended dose of lurbinectedin is 3.2 mg/square meters by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Lurbinectedin is available as a 4mg single dose vial for reconstitution.
Lurbinectedin should be administered as an intravenous infusion by a healthcare professional.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Lurbinectedin for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the use of Lurbinectedin in any indication or circumstance not described above is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective January 2023 through September 2023
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
The use of lurbinectedin meets member benefit primary coverage criteria that there be scientific evidence of effectiveness for adult individuals with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy (FDA Zepzelca, 2020) when ALL the following criteria are met:
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
The recommended dose of lurbinectedin is 3.2mg/square meter by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Lurbinectedin is available as a 4mg single dose vial for reconstitution.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Lurbinectedin for any indication or circumstance not described aboce, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving outcomes.
For members with contracts without primary coverage criteria, the use of Lurbinectedin in any indication or circumstance not described above is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective January 2022 to December 2022
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
The use of lurbinectedin meets member benefit primary coverage criteria that there be scientific evidence of effectiveness for adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy (FDA Zepzelca, 2020) when ALL the following criteria are met:
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosage and Administration
The recommended dose of lurbinectedin is 3.2mg/m2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Lurbinectedin is available as a 4mg single dose vial for reconstitution.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Lurbinectedin does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any other indication.
For members with contracts without primary coverage criteria, the use of Lurbinectedin in any other condition than listed above is considered
investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective January 2021-January 2022
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
The use of lurbinectedin meets member benefit primary coverage criteria that there be scientific evidence of effectiveness for adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy when ALL the following criteria are met:
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
NCCN 1 and 2A recommendations in accordance with Coverage Policy #2000030.
Dosage and Administration
The recommended dose of lurbinectedin is 3.2mg/m2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Lurbinectedin is available as a 4mg single dose vial for reconstitution.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Lurbinectedin does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any other indication.
For members with contracts without primary coverage criteria, the use of Lurbinectedin in any other condition than listed above is considered
investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
Lurbinectedin for the treatment of adult patients with metastatic SCLC was studied in a multicenter, open-label, multi-cohort trial. A cohort of 105 patients with SCLC with disease progression on or after platinum-based chemotherapy received single agent lurbinectedin 3.2mg/m2 by intravenous infusion every 21 days (one cycle). The minimum interval between any previous chemotherapy was 3 weeks. The primary endpoint was overall response rate. Secondary endpoints included duration of response, progression free survival, and overall survival. Patients received a median of four cycles of Lurbinectedin and 44% of patients received 6 cycles or more. The Lurbinectedin dose was delayed in 22% of patients and reduced in 26% of patients due to treatment-related adverse events. Neutropenia was the most common adverse event. The overall response rate was 35% and 0% of patients experienced complete response. The median duration of response was 5.3 months. 43% of patients were still responding to Lurbinectedin treatment at 6 months. The median progression free survival was 3.5 months and 6-month progression-free survival rate was 32.9%. Serious adverse reactions including pneumonia, febrile neutropenia, neutropenia, respiratory tract infection, anemia, dyspnea, and thrombocytopenia occurred in 34% of patients. Permanent discontinuation occurred in two patients due to adverse reactions. (Zepzelca, 2020)
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2022. No new literature was identified that would prompt a change in the coverage statement.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2023. No new literature was identified that would prompt a change in the coverage statement.
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement.
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2025. No new literature was identified that would prompt a change in the coverage statement.
2026 Update
The FDA approval as first line component in extensive stage small cell lung cancer is based on results from the Phase 3 IMforte trial (NCT05091567), which showed that the lurbinectedin and atezolizumab combination reduced the risk of disease progression or death by 46% and the risk of death by 27%, compared to atezolizumab maintenance therapy alone. Following four cycles of induction therapy, from the point of randomization the median overall survival (OS) for the lurbinectedin and atezolizumab regimen was 13.2 months versus 10.6 months for atezolizumab alone (stratified hazard ratio [HR]=0.73; 95% CI: 0.57–0.95; p=0.0174). From the point of randomization, median progression-free survival (PFS) by independent assessment was 5.4 months versus 2.1 months, respectively (stratified HR=0.54, 95% CI: 0.43–0.67; p<0.0001). These results were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The Lancet.
The most common adverse reactions for lurbinectedin in combination with atezolizumab including laboratory abnormalities, (≥ 30%) are decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased leukocytes, decreased neutrophils, nausea, and fatigue/asthenia.
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| CPT/HCPCS: | |
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| References: |
National Comprehensive Cancer Network (NCCN), Inc.(2022) . NCCN Clinical Practice Guidelines in Oncology- Small Cell Lung Cancer. NCCN Clinical Practice Guidelines in Oncology- Small Cell Lung Cancer v.1.2022. Revised August 9, 2021. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed September 30, 2021. NCCN Clinical Practice Guidelines in Oncology™. © 2020 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on January 5, 2021. Small Cell Lung Cancer. V1.2021. Revised August 11, 2020. Trigo J, et al.(2020) Lurbinectedin as Second-Line Treatment for Patients With Small-Cell Lung Cancer: A Single-Arm, Open-Label, Phase 2 Basket Trial. Lancet Oncol. 2020; 21(5):645-654. Zepelca(2023) package insert Palo Alto, CA. Jazz Pharmaceuticals, Inc.; 2023 Zepzelca [package insert] Palo Alto, CA. Jazz Pharmaceuticals, Inc.; 2020 |
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| Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants. | |
| CPT Codes Copyright © 2026 American Medical Association. | |