CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Germline and Somatic Biomarker Testing (Including Liquid Biopsy) for Targeted Treatment and Immunotherapy in Breast Cancer

Defines medical necessity and coverage stance for PIK3CA biomarker testing (including tissue and plasma/ctDNA assays and specific PLA tests) to guide targeted therapy in advanced or high‑risk breast cancer for Blue Cross Blue Shield - Rhode Island members.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyGermline and Somatic Biomarker Testing (Including Liquid Biopsy) for Targeted Treatment and Immunotherapy in Breast Cancer

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective DateJan 1, 2024

Next Review DateN/A

Key ActionOrder PIK3CA testing (tissue preferred; plasma ctDNA acceptable) to determine eligibility for alpelisib in HR+ HER2‑ advanced or metastatic breast cancer after progression on endocrine therapy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≈40%PIK3CA frequency

0155U,0177UPLA codes

AlpelisibTargeted therapy

Tissue preferredSpecimen preference

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Coverage Criteria

PIK3CA testing to select targeted therapy

Covered when ALL of the following are met

Eligibility for PIK3CA testing to guide alpelisib: Individual has hormone receptor-positive, HER2-negative advanced or metastatic breast cancer AND has progressed on or after an endocrine-based regimen

PIK3CA testing may be medically necessary to predict response to alpelisib (Piqray).

Specimen type: Testing may be performed on tumor tissue (preferred when available) OR plasma circulating tumor DNA (ctDNA)

If ctDNA is negative and tumor tissue is available, tumor tissue testing should be performed to detect additional PIK3CA mutations.

PIK3CA testing of tumor tissue for individuals with breast cancer in situations that do not meet the specific medical criteria in this policy is not covered for Medicare Advantage Plans and is considered not medically necessary for Commercial Products. Benefits and coverage may vary by contract; refer to the member's Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for plan-specific determinations.

PIK3CA testing performed for indications other than to identify eligibility for alpelisib plus endocrine therapy in hormone receptor‑positive, HER2‑negative advanced or metastatic breast cancer (after progression on or after an endocrine‑based regimen) is considered not covered or not medically necessary depending on product type and contract. Some genetic services may additionally be excluded for self‑funded groups per contract; consult coding and contract documents for details.

Covered Indications

Testing to identify PIK3CA mutations to determine eligibility for alpelisib plus endocrine therapy in HR+ HER2‑ advanced or metastatic breast cancer after progression on endocrine therapy.

Covered when ALL of the following are met

Covered indication: Testing is ordered to identify PIK3CA mutations to determine eligibility for alpelisib plus endocrine therapy in individuals with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer who have progressed on or after an endocrine-based regimen

This indication aligns with guideline recommendations to use tumor NGS or ctDNA to determine eligibility for alpelisib; if ctDNA is negative and tissue is available, tissue testing is recommended.

Acceptable assays/specimens: Use of validated assays on tumor tissue (therascreen PIK3CA RGQ PCR Kit; PLA 0155U) OR plasma ctDNA assay (therascreen PIK3CA RGQ PCR Kit; PLA 0177U)

PLA codes 0155U (tissue) and 0177U (plasma) are listed as medically necessary when the clinical criteria are met.

Eligibility Requirements

Eligibility for PIK3CA testing under this policy is limited to individuals with hormone receptor‑positive, HER2‑negative advanced or metastatic breast cancer who have progressed on or after an endocrine‑based regimen and for whom testing would determine eligibility for treatment with the PI3K inhibitor alpelisib plus endocrine therapy.

When testing is performed to guide alpelisib therapy, tumor tissue is preferred when available; plasma circulating tumor DNA (ctDNA) is an acceptable alternative, but if ctDNA is negative and tumor tissue is available, tissue testing should be performed.

Coding

Covered PLA/CPT Codes (tissue)CPTCovered

0155U

Oncology (breast cancer), DNA, PIKSCA (phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha) gene analysis utilizing formalin-fixed paraffin-embedded breast tumor tissue, reported as PIK3CA gene mutation status (PLA code for the therascreen PIK3CA RGQ PCR Kit from QIAGEN)

Covered PLA/CPT Codes (plasma/ctDNA)CPTCovered

0177U

Oncology (breast cancer), DNA, PIKSCA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) gene analysis of 11 gene variants utilizing plasma, reported as PIK3CA gene mutation status (PLA code for the therascreen PIK3CA RGQ PCR Kit from QIAGEN)

Provider Actions & Billing Notes

Prior Authorization

Prior Authorization for PLA CPT Codes

Authorization may be required for Proprietary Laboratory Analysis (PLA) CPT codes used for PIK3CA testing. Confirm prior authorization requirements before performing or billing for PLA codes 0155U and 0177U.

PLA CPT codes: 0155U, 0177U

Note

PIK3CA Testing Indication

PIK3CA testing of tumor tissue is indicated to determine eligibility for alpelisib (Piqray) in individuals with hormone receptor‑positive, HER2‑negative advanced or metastatic breast cancer who have progressed on or after an endocrine‑based regimen.

Indication: assess PIK3CA mutation status to guide alpelisib therapy after progression on endocrine‑based regimen

Billing Rule

PIK3CA Tissue Testing Preference and Limitations

When tumor tissue is available, testing of tissue is preferred for PIK3CA analysis, but plasma testing may be used when tissue is not available. PIK3CA testing of tissue in other clinical situations is considered not covered for Medicare Advantage Plans and not medically necessary for Commercial Products.

Tissue preferred when available
Tissue testing not covered in other situations for Medicare Advantage; not medically necessary for Commercial Products

Documentation Required

Benefits and Eligibility Determination

Benefits and eligibility for PIK3CA testing are determined by the member's subscriber agreement, Evidence of Coverage/Benefit Booklet, or employer agreement. For plan‑specific coverage, consult the member's benefit booklet or contact the provider call center.

Verify benefits and eligibility in the member's subscriber agreement or benefit booklet
Contact provider call center for member‑specific information

Not Covered

Genetic services or testing that are excluded by a self‑funded group contract are not covered for members of that group. Additionally, tests or services listed as not medically necessary in the Coding or Genetic Services/Proprietary Laboratory Analyses policies (including PIK3CA testing when performed outside the covered indications) are considered not covered or not medically necessary per product and contract terms. Providers should verify member benefits and any contract exclusions prior to ordering.

Background

Alterations in the PIK3CA gene occur in approximately 40% of patients with hormone receptor‑positive, HER2‑negative breast cancer. Clinical practice guidelines and FDA‑approved indications support testing (next‑generation sequencing of tumor tissue or ctDNA) to identify PIK3CA mutations when considering treatment with the PI3K inhibitor alpelisib plus endocrine therapy. When ctDNA testing is negative and tumor tissue is available, reflex tissue testing is recommended because tissue testing can detect additional actionable mutations.

Definitions

PIK3CA — definition and clinical relevance

GenePIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha)

Clinical relevanceAlterations occur in approximately 40% of HR-positive, HER2‑negative breast cancers and can be actionable to guide targeted therapy with the PI3K inhibitor alpelisib (Piqray).

Recommended testing contextTesting indicated for individuals with hormone receptor‑positive, HER2‑negative advanced or metastatic breast cancer to determine eligibility for alpelisib after progression on or after an endocrine‑based regimen.

Specimen preferenceTumor tissue testing is preferred when available; plasma (ctDNA) testing is an acceptable alternative with reflex to tissue if ctDNA is negative and tissue is available.

Guideline supportASCO (2022) recommends NGS of tumor tissue or ctDNA to identify PIK3CA mutations for patients who are candidates for a PI3K inhibitor plus hormonal therapy; if ctDNA is negative, test tumor tissue when available.

PLA codes 0155U / 0177U — proprietary laboratory analysis codes for Therascreen PIK3CA assays

0155UPLA code for Therascreen PIK3CA RGQ PCR Kit — oncology (breast cancer), DNA, PIK3CA gene analysis using formalin‑fixed paraffin‑embedded tumor tissue; reported as PIK3CA gene mutation status.

0177UPLA code for Therascreen PIK3CA RGQ PCR Kit — oncology (breast cancer), DNA, PIK3CA gene analysis of 11 variants utilizing plasma (ctDNA); reported as PIK3CA gene mutation status.

Assay vendorQIAGEN (Therascreen PIK3CA RGQ PCR Kit)

Coverage noteThese PLA CPT codes are addressed in the policy and are medically necessary only when the medical criteria for PIK3CA testing (to guide alpelisib therapy) are met.