Proteomic Testing for Targeted Therapy in Non-Small-Cell Lung Cancer Form

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 1 (401) 274-4848 WWW.BCBSRI.COM

EFFECTIVE DATE: 01|01|2024 POLICY LAST REVIEWED: 01|08|2025

OVERVIEW Proteomic testing has been proposed as a way to predict survival outcomes, as well as the response to and selection of targeted therapy for patients with non-small-cell lung cancer (NSCLC). One commercially available test (the VeriStrat assay) has been investigated as a predictive marker for response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.

The following test(s) is addressed in this policy: • VeriStrat® (Biodesix) CPT code 81538

MEDICAL CRITERIA Not applicable

PRIOR AUTHORIZATION Not applicable

POLICY STATEMENT Medicare Advantage Plans and Commercial Products The use of proteomic testing in the management of non-small-cell lung cancer may be considered medically necessary for the following test; • VeriStrat® (Biodesix) CPT code 81538

Note: Laboratories are not allowed to obtain clinical authorization or participate in the authorization process on behalf of the ordering physician. Only the ordering physician shall be involved in the authorization, appeal or other administrative processes related to prior authorization/medical necessity.

In no circumstance shall a laboratory or a physician/provider use a representative of a laboratory or anyone with a relationship to a laboratory and/or a third party to obtain authorization on behalf of the ordering physician, to facilitate any portion of the authorization process or any subsequent appeal of a claim where the authorization process was not followed and/or a denial for clinical appropriateness was issued, including any element of the preparation of necessary documentation of clinical appropriateness. If a laboratory or a third party is found to be supporting any portion of the authorization process, BCBSRI will deem the action a violation of this policy and severe action will be taken up to and including termination from the BCBSRI provider network. If a laboratory provides a laboratory service that has not been authorized, the service will be denied as the financial liability of the participating laboratory and may not be billed to the member.

Commercial Products Some genetic testing services are not covered and a contract exclusion for any self-funded group that has excluded the expanded coverage of biomarker testing related to the state mandate, R.I.G.L. §27-19- 81 described in the Biomarker Testing Mandate policy. For these groups, a list of which genetic testing services are covered with prior authorization, are not medically necessary or are not covered because they are a contract exclusion can be found in the Coding section of the Genetic Testing Services or Proprietary Laboratory Analyses policies. Please refer to the appropriate Benefit Booklet to determine whether the member’s plan has customized benefit coverage. Please refer to the list of Related Policies for more information.

Medical Coverage Policy | Proteomic Testing for Targeted Therapy in Non-Small-Cell Lung Cancer

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 2 (401) 274-4848 WWW.BCBSRI.COM

COVERAGE Benefits may vary between groups and contracts. Please refer to the appropriate Benefit Booklet, Evidence of Coverage or Subscriber Agreement for applicable laboratory benefits/coverage.

BACKGROUND Lung cancer is the leading cause of cancer death in the U.S., with an estimated 234,580 new cases and 125,070 deaths due to the disease in 2024. NSCLC accounts for approximately 80% of lung cancer cases and includes nonsquamous carcinoma (adenocarcinoma, large cell carcinoma, other cell types) and squamous cell carcinoma. The stage at which lung cancer is diagnosed has the greatest impact on prognosis. Localized disease confined to the primary site has a 59.8% relative 5-year survival but accounts for only 18% of lung cancer cases at diagnosis. Mortality increases sharply with advancing stage. Metastatic lung cancer has a relative 5-year survival of 6.3%. Overall, advanced disease, defined as regional involvement and metastatic, accounts for approximately 80% of cases of lung cancer at diagnosis. These statistics are mirrored for the population of NSCLC, with 85% of cases presenting as advanced disease and up to 40% of patients with metastatic disease. In addition to tumor stage, age, sex, and performance status are independent prognostic factors for survival particularly in early-stage disease. Wheatley-Price et al (2010) reported on a retrospective pooled analysis of 2349 advanced NSCLC patients from 5 randomized chemotherapy trials. Women had a higher response rate to platinum-based chemotherapy than men. Additionally, women with adenocarcinoma histology had greater overall survival than men. A small survival advantage exists for squamous cell carcinoma over non-bronchiolar nonsquamous histology. The oncology clinical care and research community use standard measures of performance status: Eastern Cooperative Oncology Group scale and Karnofsky Performance Scale. Treatment approaches are multimodal and generally include surgery, radiotherapy, and chemotherapy (either alone or in combination with another treatment, depending on disease stage and tumor characteristics). Per the National Comprehensive Cancer Network (NCCN) guidelines, the clinical management pathway for stage I or II NSCLC is dependent on surgical findings and may involve resection, radiotherapy, chemotherapy, or chemoradiation. First-line chemotherapy regimens for neoadjuvant and adjuvant therapy utilize platinum-based agents (eg, cisplatin, carboplatin) in combination with other chemotherapeutics and/or radiotherapy. Treatment recommendations are based on the overall health or performance status of the patient, presence or absence of metastases, as well as the presence or absence of a treatment-sensitizing genetic variant. These aspects inform the selection of targeted and systemic therapies. For patients who experience disease progression following initial systemic therapy, subsequent treatment regimens are recommended, mainly featuring novel programmed death-ligand 1 (PD-L1) inhibitors. The NCCN also includes recommendations for targeted therapy or immunotherapy in patients with biomarkers, including sensitizing epidermal growth factor receptor (EGFR) mutations. For patients with sensitizing EGFR mutations, recommendations include first-line therapy with EGFR tyrosine kinase inhibitors (TKIs) afatinib, erlotinib, dacomitinib, gefitinib, erlotinib plus ramucirumab, erlotinib plus bevacizumab (nonsquamous), or osimertinib and subsequent therapy with osimertinib. The NCCN does not make any recommendations for the use of EGFR TKIs in the absence of a confirmed sensitizing EGFR mutation. Initial systemic therapy recommendations can be considered for multiple, symptomatic, systemic lesions.

CODING Medicare Advantage Plans and Commercial Products The following CPT code(s) is covered when filed with an ICD-10 diagnosis code(s)* listed below:

This code can be used for the VeriStrat® (Biodesix) 81538 Oncology (lung), mass spectrometric 8-protein signature, including amyloid A, utilizing serum, prognostic and predictive algorithm reported as good versus poor overall survival.

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 3 (401) 274-4848 WWW.BCBSRI.COM

ICD-10 diagnosis code(s)* C33 C34-C34.92 C38.4 C45.0

RELATED POLICIES Biomarker Testing Mandate
Genetic Testing Services

PUBLISHED Provider Update, March 2025 Provider Update, October 2024 Provider Update, November 2023

REFERENCES

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500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 4 (401) 274-4848 WWW.BCBSRI.COM

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500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 5 (401) 274-4848 WWW.BCBSRI.COM

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500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 6 (401) 274-4848 WWW.BCBSRI.COM

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    This medical policy is made available to you for informational purposes only. It is not a guarantee of payment or a substitute for your medical judgment in the treatment of your patients. Benefits and eligibility are determined by the member's subscriber agreement or member certificate and/or the employer agreement, and those documents will supersede the provisions of this medical policy. For information on member-specific benefits, call the provider call center. If you provide services to a member which are determined to not be medically necessary (or in some cases medically necessary services which are non-covered benefits), you may not charge the member for the services unless you have informed the member and they have agreed in writing in advance to continue with the treatment at their own expense. Please refer to your participation agreement(s) for the applicable provisions. This policy is current at the time of publication; however, medical practices, technology, and knowledge are constantly changing. BCBSRI reserves the right to review and revise this policy for any reason and at any time, with or without notice. Blue Cross & Blue Shield of Rhode Island is an independent licensee of the Blue Cross and Blue Shield Association.

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