Coverage Policy Manual
Policy #: 2021001
Category: Pharmacy
Initiated: January 2021
Last Review: January 2025
  Lurbinectedin (e.g., Zepzelca)
Description:
Lurbinectedin 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)
 
Coding
 
See CPT/HCPCS Code section below.
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).
 
The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
Effective January 2025
 
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:
 
1. Individual is diagnosed with metastatic small cell lung cancer (SCLC) (Zepzelca, 2023); AND
2. Individual is 18 years of age or older (Zepzelca, 2023); AND
3. Individual is using as a single agent (Trigo, 2020; NCCN 2A); AND
4. Individual has a current ECOG performance status of 2 or lower (see policy guidelines) (NCCN 2 A); AND
5. Individual experienced disease progression on or after platinum-based chemotherapy (Zepzelca, 2023); OR
6. Individual with relapse within 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
7. Individual with relapse occurring more than 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
8. Individual with primary progressive disease (NCCN 2A); AND
9. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
1. Submission of clinical documentation showing stability and/or improvement in condition; AND
2. Is being dosed according to the FDA guidelines.
 
Policy Guidelines
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
    • 0 = Fully active, able to carry on all pre-disease performance without restriction
    • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
    • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
    • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
    • 5 = Dead
 
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:
 
1. Individual is diagnosed with metastatic SCLC (FDA Zepzelca, 2020); AND
2. Individual is 18 years of age or older (FDA Zepzelca, 2020); AND
3. Individual is using as a single agent (Trigo, 2020); AND
4. Individual has a current ECOG performance status of 2 or lower (NCCN 2 A).
5. Individual experienced disease progression on or after platinum-based chemotherapy (FDA Zepzelca, 2020); OR
6. Individual with relapse within 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
7. Individual with relapse occurring more than 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
8. Individual with primary progressive disease (NCCN 2A); AND
9. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
1. Submission of clinical documentation showing stability and/or improvement condition.
2. Is being dosed according to the FDA guidelines.
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
 
    • 0 = Fully active, able to carry on all pre-disease performance without restriction
    • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
    • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
    • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
    • 5 = Dead
 
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:
 
  1. Individual is diagnosed with metastatic SCLC (FDA Zepzelca, 2020); AND
  2. Individual is 18 years of age or older (FDA Zepzelca, 2020); AND
  3. Individual is using as a single agent (Trigo, 2020) ;AND
  4. Individual has a current ECOG performance status of 2 or lower (NCCN 2 A);
  5. Individual experienced disease progression on or after platinum-based chemotherapy (FDA Zepzelca, 2020); OR
  6. Individual with relapse within 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
  7. Individual with relapse occurring more than 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
  8. Individual with primary progressive disease (NCCN 2A).
  9. Must be dosed in accordance with the FDA label.
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
 
  • 0 = Fully active, able to carry on all pre-disease performance without restriction
  • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
  • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
  • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
  • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
  • 5 = Dead
 
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:
 
        1. Member is diagnosed with metastatic SCLC (FDA Zepzelca, 2020); AND
        2. Member is 18 years of age or older (FDA Zepzelca, 2020); AND
        3. Member is using as a single agent (Trigo, 2020) ;AND
        4. Member has a current ECOG performance status of 2 or lower (NCCN 2 A);
        5. Member experienced disease progression on or after platinum-based chemotherapy (FDA Zepzelca, 2020); OR
        6. Member with relapse within 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
        7. Member with relapse occurring more than 6 months following complete or partial response or stable disease with primary treatment (NCCN 2A); OR
        8. Member with primary progressive disease (NCCN 2A).
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
 
        • 0 = Fully active, able to carry on all pre-disease performance without restriction
        • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work
        • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
        • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
        • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
        • 5 = Dead
 
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:
 
    1. Member is diagnosed with metastatic SCLC AND
    2. Member is 18 years of age or older AND
    3. Member is using as a single agent AND
    4. Member experienced disease progression on or after platinum-based chemotherapy AND  
    5. Member has a current ECOG performance status of 2 or lower
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
 
    • 0 = Fully active, able to carry on all pre-disease performance without restriction
    • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work
    • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
    • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
    • 5 = Dead
 
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.
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.
CPT/HCPCS:
J9223Injection, lurbinectedin, 0.1 mg
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.

Zepzelca [package insert] Palo Alto, CA. Jazz Pharmaceuticals, Inc.; 2020
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.