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Lurbinectedin (Zepzelca®)
08.01.67c

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Lurbinectedin (Zepzelca®​) is considered medically necessary and, therefore, covered as a single agent for the ​subsequent treatment of adult individuals with ​advanced or metastatic small cell lung cancer (SCLC) when all of the following criteria are met:
  • Individual has had disease progression on or after platinum-based chemotherapy
  • Individual is classified as being in one of the following stages:​
    • Relapse following complete or partial response or stable disease with primary treatment 
    • Primary progressive disease 
  • Individual has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2
MANDATES 
 
PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.​

EXPERIMENTAL/INVESTIGATIONAL

All other uses for lurbinectedin (Zepzelca) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics. 

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

Guidelines

​BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, lurbinectedin (Zepzelca​) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

THE EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG) has developed the ECOG performance status. It was originally published in 1982 in the American Journal of Clinical Oncology*. ECOG states, "These scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. They are included here for health care professionals to access."

ECOG Performance Status
Grade
ECOG
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, e.g., 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 percent of waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self-care: Totally confined to bed or chair
5
Dead
*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

​
US FOOD AND DRUG ADMINISTRATION STATUS

Lurbinectedin (Zepzelca) was approved by the US Food and Drug Administration (FDA) on June 15, 2020, for the treatment of adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. This indication 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. 

From the product's prescribing information: The recommended dosage of lurbinectedin (Zepzelca) for SCLC is 3.2 mg/m2 by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity. Initiate treatment with lurbinectedin (Zepzelca) only if absolute neutrophil count (ANC) is at least 1,500 cells/mm3 and platelet count is at least 100,000/mm3.

PEDIATRIC USE
The safety and effectiveness of lurbinectedin (Zepzelca) in pediatric individuals have not been established.

Description

SMALL CELL LUNG CANCER 

Lung cancer is the second most common cancer and the leading cause of cancer death among women and men in the United States. Small cell lung cancer (SCLC) accounts for 10 percent to15 percent of all lung cancers. SCLC is distinguished from non-small cell lung cancer (NSCLC) by its rapid doubling time, high growth fraction, and the early development of widespread metastases. SCLC is diagnosed almost exclusively in individuals who smoke.

LURBINECTEDIN (ZEPZELCA)

Lurbinectedin (Zepzelca) was approved by the US Food and Drug Administration (FDA) on June 15, 2020, for the treatment of adults with metastatic small cell lung cancer (SCLC) who had disease progression on or after platinum-based chemotherapy.

Lurbinectedin (Zepzelca) is an alkylating drug and a selective inhibitor of oncogenic transcription that preferentially binds to guanine residues in the DNA and affects the activity of DNA-binding proteins, resulting in the disruption of the tumor cell cycle and eventual tumor cell death (apoptosis). Tumors can prevent macrophages from performing their immune response. Lurbinectedin (Zepzelca) inhibits the transcription of tumor-associated macrophages, further affecting the tumor microenvironment landscape.

PEER-REVIEWED LITERATURE
Summary

The safety and efficacy of lurbinectedin (Zepzelca) as a single agent was evaluated in a multicenter, open-label, multicohort trial in individuals with advanced or metastatic solid tumors. Trigo et al. (2020) assessed a cohort of 105 individuals with SCLC with disease progression on or after platinum-based chemotherapy. The individuals in the cohort received lurbinectedin (Zepzelca) 3.2 mg/m2 by intravenous infusion every 21 days until disease progression or unacceptable toxicity. Tumor assessments (CT scans or MRI) were conducted every 6 weeks for the first 18 weeks and every 9 weeks thereafter. Baseline characteristics included: 92 percent had Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, 92 percent were former/current smokers, and 100 percent of individuals received at least one line of platinum-based chemotherapy. Prior radiotherapy had been administered to 71 percent of individuals and 8 percent had prior immunotherapy in addition to platinum-based chemotherapy. The major efficacy outcome measure was confirmed investigator-assessed overall response rate (ORR). At the median follow-up period of 17.1 months, the investigator-assessed ORR was 35 percent (complete response 0 percent, partial response 35 percent) and the median duration of response was 5.3 months. In the assessment of overall survival, 63 percent of individuals had died and the median overall survival was 9.3 months. Serious treatment-related adverse events included neutropenia (46 percent), leucopenia (29 percent), and febrile neutropenia (5 percent).

OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Cancer Society (ACS). Key statistics for lung cancer. [ACS Web site]. 01/16/2025. Available at: https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed April 9, 2025.  

American Cancer Society (ACS). What is lung cancer? [ACS Web site]. 01/29/2024.  Available at: https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed April 9, 2025. 

American Hospital Formulary Service (AHFS). Lurbinectedin (Zepzelca®). AHFS Drug Information 2025. [UpToDate LexiDrug Web site]. 02/17/2025. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed April 9, 2025.  

Byers LA, Gay CM. Pathobiology and staging of small cell carcinoma of the lung. [UpToDate Web site]. 01/17/2025. Available at: https://www.uptodate.com/contents/pathobiology-and-staging-of-small-cell-carcinoma-of-the-lung?search=Pathobiology and staging of small cell carcinoma of the lung&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 [via subscription only]. Accessed April 9, 2025.

Elsevier's Clinical Pharmacology Compendium. Lurbinectedin (Zepzelca®). 02/12/2025. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed April 9, 2025.  

Lurbinectedin (Zepzelca®) [prescribing information]. 07/2023. Palo Alto, CA: Jazz Pharmaceuticals, Inc. Available at: https://www.zepzelca.com/. Accessed April 9, 2025.  

Merative Micromedex® DRUGDEX® (electronic version). Lurbinectedin (Zepzelca®). [Micromedex Web site]. 02/11/2025. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed April 9, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology®. Small cell lung cancer, V4.2025. [NCCN Web site]. 01/13/2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf [via free subscription only]. Accessed April 9, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium®. [NCCN Web site]. Lurbinectedin (Zepzelca®). Available at: http://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed April 9, 2025.

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

Trigo J, Subbiah V, Besse B, et al. 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.

UpToDate® LexidrugTM. Lurbinectedin (Zepzelca®). [UpToDate Lexidrug Web site]. 02/18/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed April 9, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Lurbinectedin (Zepzelca®). Prescribing information. [FDA Web site]. 07/28/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed April 9, 2025.  

Coding

CPT Procedure Code Number(s)
N/A
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)
C33Malignant neoplasm of trachea 
C34.00Malignant neoplasm of unspecified main bronchus
C34.01 Malignant neoplasm of right main bronchus
C34.02Malignant neoplasm of left main bronchus
C34.10Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11Malignant neoplasm of upper lobe, right bronchus or lung
C34.12Malignant neoplasm of upper lobe, left bronchus or lung
C34.2Malignant neoplasm of middle lobe, bronchus or lung
C34.30Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.31Malignant neoplasm of lower lobe, right bronchus or lung
C34.32Malignant neoplasm of lower lobe, left bronchus or lung
C34.80Malignant neoplasm of overlapping sites of unspecified bronchus and lung
C34.81Malignant neoplasm of overlapping sites of right bronchus and lung
C34.82Malignant neoplasm of overlapping sites of left bronchus and lung
C34.90Malignant neoplasm of unspecified part of unspecified bronchus or lung
C34.91Malignant neoplasm of unspecified part of right bronchus or lung
C34.92Malignant neoplasm of unspecified part of left bronchus or lung



HCPCS Level II Code Number(s)
​J9223 Injection, lurbinectedin, 0.1 mg
Revenue Code Number(s)
N/A





Coding and Billing Requirements

​

Policy History

Revisions From ​08.01.67c:
​05/28/2025
​This policy has been reviewed and reissued to communicate the Company’s continuing position on lurbinectedin (Zepzelca®​)​.​
10/30/2024
​The policy has been reviewed and reissued to communicate the Company’s continuing position on lurbinectedin (Zepzelca®​)​.
05/08/2023​This version of the policy will become effective 05/08/2023​.​​

This policy has been updated to communicate the Company's coverage position for lurbinectedin (Zepzelca), in alignment with US Food and Drug Administration (FDA) and National Comprehensive Cancer Network (NCCN). The options for subsequent therapy are now recommended regardless of the time since relapse.

Revisions From 08.01.67b:
​04/20/2022
​This policy has been reissued in accordance with the Company's annual review process.​
05/24/2021

This version of the policy will become effective 05/24/2021​.


This policy has been updated to communicate the Company's coverage position for lurbinectedin (Zepzelca), in alignment with US Food and Drug Administration (FDA) and National Comprehensive Cancer Network (NCCN).


​Revisions From 08.01.67a:
01/01/2021
This policy has been identified for the HCPCS code update, effective 01/01/2021.

The following NOC codes have been removed from this policy and are replaced by the following HCPCS code:

REMOVED:  

C9399 Unclassified drugs or biologicals
J3490 Unclassified drugs
REPLACED WITH: J9223 Injection, lurbinectedin, 0.1 mg


Revisions From 08.01.67:
09/14/2020The following new policy has been developed to communicate the Company's coverage criteria for lurbinectedin (ZepzelcaTM).

5/8/2023
5/8/2023
5/28/2025
08.01.67
Medical Policy Bulletin
Commercial
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Independence Blue Cross is a subsidiary of Independence Health Group, Inc. — independent licensees of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.