Viva Health pertuzumab Coverage & Prior Auth

Coverage Criteria for Pertuzumab (Perjeta)

Initial Therapy - Breast Cancer

Covered when ALL of the following are met

Universal criteria: Patient is ≥ 18 years of age; Left ventricular ejection fraction (LVEF) is within normal limits prior to initiating therapy and will be assessed at regular intervals (e.g., every 3 months) during treatment; Patient has HER2-positive disease as determined by an FDA-approved or CLIA-compliant test; Therapy will not be used in combination with pertuzumab/trastuzumab and hyaluronidase-zzxf (Phesgo).

See tumor-specific HER2 testing definitions in document.

Breast cancer indications: Neoadjuvant/preoperative therapy for patients with ≥ T1c disease, node positive disease, or inflammatory disease, used in combination with trastuzumab and chemotherapy; OR Adjuvant therapy for patients with ≥ T1 disease, node positive disease, or inflammatory disease used in combination with trastuzumab and chemotherapy (pT2-3 and pN0 or pN+ only) or in combination with trastuzumab per specified pathologic stages; OR Used after completion of planned chemotherapy and surgery for patients with ≥ ypT0N0/pCR disease by axillary staging in combination with trastuzumab; OR Recurrent unresectable, metastatic, or inflammatory breast cancer: used as first-line therapy in combination with trastuzumab and either paclitaxel or docetaxel, OR used as subsequent therapy in combination with trastuzumab with or without cytotoxic therapy provided the patient was previously treated with trastuzumab and chemotherapy and has not previously received pertuzumab.

Neoadjuvant/adjuvant treatment limited to a total duration of one year (up to 18 cycles).

Initial Therapy - CNS (brain metastases)

Covered when ALL of the following are met

CNS metastases (breast cancer): Used for the treatment of brain metastases from breast cancer in combination with trastuzumab; appropriate scenarios include initial treatment for small asymptomatic brain metastases, relapsed limited brain metastases with stable systemic disease or reasonable systemic treatment options, recurrent limited brain metastases, or recurrent extensive brain metastases with stable systemic disease or reasonable systemic treatment options.

Initial/Subsequent Therapy - Colorectal / Appendiceal

Covered when ALL of the following are met

Colorectal/Appendiceal adenocarcinoma: RAS and BRAF wild-type disease with HER2 amplification used in combination with trastuzumab; indications include initial treatment for unresectable metastatic disease when prior FOLFOX or CapeOX was given within the past 12 months, primary treatment for unresectable or metastatic disease when intensive therapy is not recommended, or subsequent therapy for progression of advanced/metastatic disease provided the patient has not previously received HER2-targeted therapy.

NCCN recommends universal MMR/MSI testing; consider checkpoint inhibitor therapy if dMMR/MSI-H when appropriate.

Initial/Subsequent Therapy - Head and Neck

Covered when ALL of the following are met

Head and neck (salivary gland): Patient has salivary gland tumors and therapy is used in combination with trastuzumab for recurrent disease, defined as distant metastases, unresectable locoregional recurrence with prior radiation therapy, or an unresectable second primary with prior radiation therapy.

Subsequent Therapy - Biliary Tract

Covered when ALL of the following are met

Biliary tract cancers: Used as subsequent treatment for progression on or after systemic treatment for unresectable, gross residual (R2), or metastatic biliary tract disease (including gallbladder and intra-/extra-hepatic cholangiocarcinoma) in combination with trastuzumab.

Therapy will not be authorized when ordered in combination with pertuzumab/trastuzumab and hyaluronidase-zzxf (Phesgo). This exclusion is part of the universal eligibility criteria and applies regardless of tumor type or line of therapy.

For Medicare members, this policy is intended for non‑Medicare coverage determinations; where applicable, Medicare NCDs, LCDs, and LCAs take precedence. Providers must follow CMS guidance for Part B drugs (Medicare Benefit Policy Manual, Pub. 100-2, Ch. 15, §50) and comply with any relevant NCD/LCD/LCA requirements when submitting claims or requesting authorization.

Use of pertuzumab for metastatic breast cancer as a subsequent-line therapy is allowed only when the patient has not previously received pertuzumab. For subsequent therapy after progression, prior treatment with trastuzumab and chemotherapy is required, and pertuzumab may be used in combination with trastuzumab with or without cytotoxic agents.

Billing and Diagnosis Codes

Covered HCPCS CodesHCPCSCovered

J9306

Injection, pertuzumab, 1 mg

NDCNDC

50242-0145-xx

Perjeta 420 mg/14 mL single-dose vial for injection

Covered ICD-10 Diagnosis Codes (Appendix 1, partial)ICD-10Covered

C06.9	Malignant neoplasm of mouth, unspecified.
C07	Malignant neoplasm of parotid gland.
C08.0	Malignant neoplasm of submandibular gland.
C08.1	Malignant neoplasm of sublingual gland.
C08.9	Malignant neoplasm of major salivary gland, unspecified.
C18.0	Malignant neoplasm of cecum.
C18.1	Malignant neoplasm of appendix.
C18.2	Malignant neoplasm of ascending colon.
C18.3	Malignant neoplasm of hepatic flexure.
C18.4	Malignant neoplasm of transverse colon.

1–10 of 85

1/9

Dosing schedule

Loading dose840 mg IV x 1

Maintenance dose420 mg IV every 21 days

Maximum neoadjuvant/adjuvant durationLimited to total of 1 year (18 cycles) when used in neoadjuvant/adjuvant breast cancer

Prior Authorization, Documentation, and Operational Notes

Prior Authorization

Prior Authorization and Duration

Prior Authorization Required. Prior authorization is required for pertuzumab (Perjeta) therapies. Initial approvals are provided for 6 months and may be renewed. Neoadjuvant and adjuvant breast cancer treatment may be authorized up to a maximum of 1 year (18 cycles).

Initial authorization duration: 6 months; renewals permitted per renewal criteria.
Neoadjuvant/adjuvant breast cancer limit: up to 1 year (18 cycles).

Note

Medicare Policy Compliance and Prior Authorization

Medicare Part B coverage follows CMS policy and any applicable NCDs, LCDs, or LCAs. Providers must follow the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 and check the CMS Coverage Database for current determinations. Where Medicare guidance applies to a member, that guidance governs coverage decisions.

CMS Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 governs Part B outpatient drugs.
Search NCD/LCD/LCA: https://www.cms.gov/medicare-coverage-database/search.aspx

Regimens and Evidence-Based Indications

Regimen	Indication / Setting	Dosing / Duration	Coverage status
Pertuzumab in combination with trastuzumab and chemotherapy (e.g., paclitaxel or docetaxel)
Breast cancer: neoadjuvant, adjuvant, and metastatic settings per tumor/pathologic criteria (see criteria) — includes neoadjuvant for ≥T1c, node positive, or inflammatory disease; adjuvant for ≥T1 disease with node positive or inflammatory disease; first-line metastatic in combination with trastuzumab + paclitaxel or docetaxel; subsequent therapy when prior trastuzumab+chemotherapy and no prior pertuzumab
Loading dose 840 mg IV x1, then 420 mg IV every 21 days. Neoadjuvant: 3–9 cycles prior to surgery. Neoadjuvant/adjuvant use limited to a total of 1 year (up to 18 cycles). Metastatic: continue until disease progression or unacceptable toxicity.
covered

Regimen	Indication / Setting	Notes	Coverage status
Pertuzumab used in combination with trastuzumab
CNS metastases from breast cancer — for treatment of brain metastases (initial small asymptomatic lesions, relapsed limited metastases with stable systemic disease or reasonable systemic options, recurrent limited disease, or recurrent extensive disease with stable systemic disease)
Use in combination with trastuzumab; evidence includes phase II studies of pertuzumab combinations for progressive brain metastases
covered

Regimen	Indication / Setting	Biomarker requirement / Notes	Coverage status
Pertuzumab in combination with trastuzumab
Colorectal and appendiceal adenocarcinoma — used as initial or subsequent therapy for unresectable/metastatic disease or when intensive therapy not recommended
Requires RAS and BRAF wild-type disease and tumor HER2 amplification (per NCCN); patient should not have previously received HER2-targeted therapy for some scenarios
covered_with_criteria

Regimen	Indication / Setting	Evidence cited	Coverage status
Pertuzumab + trastuzumab + docetaxel
Metastatic HER2-positive breast cancer as first-line therapy in combination with trastuzumab and a taxane
CLEOPATRA trial cited (Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer)
covered

Regimen	Indication / Setting	Evidence / Dosing notes	Coverage status
Pertuzumab + trastuzumab + chemotherapy (neoadjuvant)
Neoadjuvant treatment for HER2-positive early/locally advanced breast cancer (e.g., patients ≥T1c, node positive, or inflammatory disease)
NeoSphere and TRYPHAENA trials cited; dosing per breast cancer: 840 mg IV x1 then 420 mg IV q21d; neoadjuvant 3–9 cycles prior to surgery; cardiac safety studies referenced
covered

Regimen	Indication / Setting	Evidence / Policy note	Coverage status
Pertuzumab + trastuzumab (tumor-agnostic for HER2-amplified tumors)
Studied across multiple tumor types with HER2 amplification (basket trials / MyPathway) including salivary gland and biliary tract tumors
Evidence from the MyPathway multiple-basket study and related reports cited; policy notes evidence but specifics of coverage vary by tumor type and criteria
experimental

Line of Therapy Designations

inv-24: first-line | subsequent

Line of therapy: Pertuzumab may be used as first-line or subsequent therapy depending on tumor type and prior treatments per the indication-specific criteria.

Refer to indication-specific nodes for details (breast: neoadjuvant, adjuvant limited to 1 year, first-line metastatic with trastuzumab+taxane, or subsequent therapy if prior trastuzumab+chemotherapy and no prior pertuzumab).

inv-25: initial | subsequent

Line of therapy: Pertuzumab may be used as initial or subsequent therapy for colorectal and appendiceal adenocarcinomas with RAS/BRAF wild-type and HER2 amplification, as specified in the indication criteria; prior HER2-targeted therapy excludes some subsequent uses.

Refer to NCCN guidance for line-specific recommendations.

Testing and Biomarker Requirements

HER2 (IHC/ISH/FISH/NGS) — tumor-specific testing definitions and thresholds

Breast, CNS, Head & Neck (tumor-specific)IHC 3+ OR dual-probe ISH HER2/CEP17 ratio ≥2.0 AND average HER2 copy number ≥4.0 signals/cell; or specified concurrent IHC/ISH combinations per tissue

Colorectal and AppendicealIHC 3+ OR FISH HER2/CEP17 ratio ≥2 with concurrent IHC 2+ OR NGS panel showing HER2 amplification

Biliary TractIHC 3+ OR dual-probe ISH HER2/CEP17 ratio ≥2.0 AND average HER2 copy number ≥4.0 signals/cell OR NGS panel HER2 amplification; concurrent IHC/ISH combinations also acceptable

RAS/BRAF — Wild-type required for HER2-targeted use (colorectal/appendiceal)

Required RAS/BRAF statusRAS and BRAF must be wild-type for use of HER2-targeted therapy in colorectal and appendiceal adenocarcinoma

Prior HER2-targeted therapy

Definitions and Reference Sources

HER2-positive disease — definition by IHC/ISH/FISH/NGS and tumor-specific criteria

General definitionHER2-positive disease: tumor-specific criteria — e.g., IHC 3+; OR dual-probe ISH HER2/CEP17 ratio ≥2.0 with average HER2 copy number ≥4.0 signals/cell; OR specified concurrent IHC/ISH combinations

Breast/CNS/Head & NeckIHC 3+ OR dual-probe ISH ratio ≥2.0 AND average HER2 copy number ≥4.0 signals/cell; or defined concurrent IHC/ISH combinations

Colorectal/Appendiceal/BiliaryAcceptable methods include IHC 3+, FISH/ISH criteria with concurrent IHC as specified, or NGS-detected HER2 amplification depending on tumor type

NCCN Compendium / Guidelines — versions cited as supporting references

NCCN Compendium (pertuzumab)NCCN Drugs & Biologics Compendium pertuzumab (2025) cited as a supporting reference

NCCN Guidelines — Breast Cancer

Policy Revision History

2025-06-05policy_reviewLatest

Policy last reviewed; document metadata lists last review date as 2025-06-05.

2012-11-01effective_date

Policy effective date established as 2012-11-01 per document metadata.

OpenPayer

Perjeta (pertuzumab) (Intravenous) Coverage Criteria

Coverage Criteria for Pertuzumab (Perjeta)

Billing and Diagnosis Codes

Prior Authorization, Documentation, and Operational Notes

Regimens and Evidence-Based Indications

Line of Therapy Designations

Testing and Biomarker Requirements

Definitions and Reference Sources

Policy Revision History