CurrentAnthemPolicy CC-0110

Pertuzumab agents (Perjeta, Poherdy) — Coverage Criteria

Clinical criteria for coverage of pertuzumab (Perjeta) and its biosimilar Poherdy for members receiving medical benefit, focusing on HER2-positive breast cancer indications and related treatment settings.

Policy Summary

PayerAnthem

PolicyPertuzumab agents (Perjeta, Poherdy) — Coverage Criteria

Policy CodePolicy CC-0110

Change TypeRevised — added biosimilar and clarified NCCN 2A uses

Effective Date01/30/2026

Next Review Date

Key ActionObtain prior authorization with documentation of HER2 positivity (IHC 3+ or ISH positive) and planned combination use with trastuzumab plus specified taxane.

SourceLink

POLICY UPDATE CHANGES

Document status updated to Revised and clinical criteria provided for Perjeta and biosimilar Poherdy.

Add new biosimilar Poherdy (pertuzumab-dpzb) to the clinical criteria and HCPCS NOC entries.

Clarify NCCN 2A recommendations for several tumor types (breast brain metastases, biliary tract, colorectal/appendiceal, salivary gland).

Added ICD-10 diagnosis codes (multiple) for cancers addressed by the policy.

18 cyclesmaximum pertuzumab duration (12-month course)

IHC 3+/ISH+HER2 positivity required

Age <19pediatric approvals

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trastuzumab + taxane

recommended combo regimen

cardiac/embryo-fetalblack box warnings

C9399, J9306, J9999HCPCS referenced

Coverage Criteria for Pertuzumab Agents

Covered with criteria

Requests for Perjeta (pertuzumab) or Poherdy (pertuzumab-dpzb) may be approved if the following are met:

Approval pathways: Approval allowed if ANY of the following main branches apply: (I) individual is under 19 years of age; OR (II) individual has HER2-positive breast cancer and meets indication-specific criteria.

See subnodes for II

HER2-positive breast cancer branch (II)

Confirmation: HER2 positivity confirmed by IHC 3+ OR ISH positive.
Allowed uses
- Metastatic first-line: Used as first-line therapy for recurrent unresectable or metastatic HER2+ breast cancer in combination with trastuzumab (or trastuzumab biosimilars) and either docetaxel or paclitaxel.
  (Label, NCCN 1, 2A)
- Metastatic progression after trastuzumab without pertuzumab: May be considered for disease progression in combination with trastuzumab (or biosimilars), with or without cytotoxic therapy (e.g., vinorelbine or taxane) for one line of therapy in individuals previously treated with chemotherapy and trastuzumab without pertuzumab.
- Neoadjuvant criteria: Neoadjuvant use prior to surgery when the primary tumor is >2 cm in diameter OR the individual is clinically node positive.
  (Label, NCCN 2A)
- Adjuvant/high-risk: Adjuvant systemic therapy when the cancer is high risk of recurrence; includes request to continue pertuzumab in combination with trastuzumab to complete 12 months after completing 6 cycles (18 weeks) of TCHP induction.
  (NCCN 2A)
- Regimen and performance: Individual must have ECOG performance status 0-2 and receive pertuzumab in combination with trastuzumab (or trastuzumab biosimilars) and either docetaxel (with or without carboplatin) or paclitaxel.
  (Label, NCCN 2A)
- Duration: Pertuzumab use in these settings is limited to a maximum of 18 cycles (12-month course).
  (NCCN 2A)

Pediatric branch (I): Individual under 19 years of age may be approved per policy pathways.

See policy authorization requirements

The available evidence does not demonstrate benefit of pertuzumab outside established HER2‑positive breast cancer settings. Multiple phase 2 studies are evaluating pertuzumab in other solid tumors and in novel combinations, but data are limited to early reports and abstracts and there are no large randomized controlled trials that establish safety and efficacy versus standard therapies for malignancies other than breast cancer. Perjeta carries important safety warnings including left ventricular dysfunction and embryo‑fetal toxicity, which are considerations when assessing off‑label uses.

Pertuzumab use should generally be in combination with trastuzumab (or trastuzumab biosimilars) in the approved HER2‑positive settings described in this policy. Requests where pertuzumab is given after trastuzumab has been discontinued, or where pertuzumab is used as part of a regimen that omits trastuzumab, are not consistent with the coverage criteria and may be denied. Clinical documentation must therefore show the intended combination with trastuzumab or a stated rationale that fits the narrow exceptions described in the criteria.

Combining pertuzumab with other targeted biologic agents that are not specifically listed in this policy is not supported by current evidence. Examples of such agents include, but are not limited to, erlotinib, cetuximab, panitumumab, bevacizumab (and its biosimilars), lapatinib, and ziv‑aflibercept. Requests proposing unlisted biologic combinations will be considered investigational and are not supported by the policy.

Requests that do not meet the criteria in this policy are not approved. This includes use of pertuzumab without documented HER2 positivity as defined in the policy, use after trastuzumab has been discontinued or in regimens that omit trastuzumab, and concomitant use with non‑listed targeted biologics. Providers should submit required HER2 test results and regimen details to support medical necessity.

Regimens and Combinations Considered Covered

Regimen	Indication / Setting	Key requirements	Duration / Notes
Pertuzumab + trastuzumab (or trastuzumab biosimilars) + docetaxel
Recurrent unresectable or metastatic HER2-positive breast cancer — first-line therapy
HER2+ confirmed; ECOG 0-2; pertuzumab given in combination with trastuzumab (or biosimilars) and docetaxel (with or without carboplatin).
Pertuzumab limited to a maximum of 18 cycles (12 months).

Regimen	Indication / Setting	Key requirements	Duration / Notes
Pertuzumab + trastuzumab (or trastuzumab biosimilars) + paclitaxel
Recurrent unresectable or metastatic HER2-positive breast cancer — first-line therapy
HER2+ confirmed; ECOG 0-2; pertuzumab given in combination with trastuzumab (or biosimilars) and paclitaxel.
Pertuzumab limited to a maximum of 18 cycles (12 months).

Permitted Lines of Therapy

first-line | adjuvant/neoadjuvant | subsequent

First-line (neoadjuvant/adjuvant/subsequent grouping): Pertuzumab use per indication as initial or adjuvant/neoadjuvant therapy: neoadjuvant when primary tumor >2 cm or node‑positive; adjuvant when high risk of recurrence; option to continue pertuzumab plus trastuzumab to complete 12 months after TCHP induction.

ECOG 0-2 and combination with trastuzumab plus taxane required where specified

Adjuvant/Neoadjuvant: Neoadjuvant: prior to surgery for tumors >2 cm or clinically node‑positive. Adjuvant: systemic therapy for high risk of recurrence; may continue after 6 cycles of TCHP to finish a 12‑month course.

(Label, NCCN 2A)

Subsequent use includes consideration for disease progression in combination with trastuzumab (with or without cytotoxic therapy) for one line of therapy in those previously treated with chemotherapy and trastuzumab without pertuzumab.

first-line | second-line | salvage

Biomarker and Diagnostic Requirements

HER2 (IHC, ISH) — required result

Required HER2 resultIHC 3+ OR ISH positive according to ASCO/CAP criteria

IHC 3+ definitionCircumferential, complete, intense membrane staining in >10% of invasive tumor cells (homogeneous/contiguous)

ISH positive numeric criteriaSingle‑probe average HER2 copy number ≥6.0 signals/cell OR dual‑probe HER2/CEP17 ratio ≥2.0 with average HER2 copy number ≥4.0 signals/cell (per ASCO/CAP)

HER2 / ERBB2 — testing & related notes

HER2 / ERBB2 requirementAll listed indications require HER2‑positive or HER2‑amplified disease (HER2/ERBB2) as specified in the criteria

Biosimilar inclusionPolicy language explicitly includes pertuzumab biosimilars (eg, Poherdy, pertuzumab‑dpzb) for indicated uses

Billing Codes and Diagnosis Codes

Provider Requirements and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests for Perjeta (pertuzumab) and Poherdy (pertuzumab-dpzb) for all covered indications. Requests submitted without prior authorization may be delayed or denied.

Prior authorization required for all listed HER2+ indications and pediatric use (individuals under 19 years of age).
Include any applicable biosimilars (Poherdy) under the same prior authorization requirement.

Documentation Required

Documentation of HER2 Status and Indication Required

Documentation must demonstrate the individual’s HER2-positive status and the covered indication for which pertuzumab is being requested. Requests that lack confirmatory HER2 testing or that propose pertuzumab outside of approved/recognized therapy settings may be denied.

HER2-positive disease confirmation (IHC 3+ or ISH positive).

Background and Rationale

Pertuzumab is a recombinant humanized monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) and is intended to inhibit HER2‑mediated signaling. It is used in combination with trastuzumab and cytotoxic chemotherapy for treatment of HER2‑positive breast cancer in neoadjuvant, adjuvant (high‑risk) and metastatic settings. Safety considerations include risk of decreased left ventricular ejection fraction and potential embryo‑fetal harm, which are described in the product labeling and summarized in this policy.

Definitions and Testing Categories

Therapy definitions

Neoadjuvant therapyTreatment given before primary surgery to shrink a tumor (eg, chemotherapy, radiation, hormone or biologic therapy)

Adjuvant therapyTreatment given after the primary treatment to increase the chances of cure or reduce recurrence risk

Line definitionsFirst‑line, second‑line and third‑line therapy defined by sequence of treatments and response (first‑line = initial primary treatment)

HER2 testing categories (ASCO/CAP)

HER2 positiveIHC 3+ OR ISH positive per ASCO/CAP (IHC 3+ = complete, intense circumferential membrane staining in >10% of invasive tumor cells)

HER2 equivocalIHC 2+ (incomplete/weak‑moderate staining >10% or intense staining ≤10%) or ISH equivocal numeric ranges (eg, singleprobe avg HER2 4.0–<6.0 signals/cell)

Policy Revision History

2026-01-30policy_publishLatest

Policy published with status 'Revised' and clinical criteria added for Perjeta (pertuzumab) and biosimilar Poherdy (pertuzumab-dpzb).

2025-12-08last_review

Last review completed prior to publication (Last Review Date recorded).

2026-01-30material_change

Policy Summary

PayerAnthem

PolicyPertuzumab agents (Perjeta, Poherdy) — Coverage Criteria

Policy CodePolicy CC-0110

Change TypeRevised — added biosimilar and clarified NCCN 2A uses

Effective Date01/30/2026

Next Review Date

Key ActionObtain prior authorization with documentation of HER2 positivity (IHC 3+ or ISH positive) and planned combination use with trastuzumab plus specified taxane.

SourceLink

On This Page

Line of therapy grouping: Pertuzumab may be used as initial systemic therapy, subsequent therapy, or for salvage depending on tumor type and NCCN 2A language; specific sequencing requirements (e.g., prior FOLFOX/CapeOX within 12 months for some colorectal scenarios and no prior HER2 inhibitor for certain initial uses) apply.

See indication‑specific criteria for details

Use across tumor typesHER2/ERBB2 positivity required for breast, biliary tract, colorectal/appendiceal, and salivary gland indications per NCCN 2A guidance

RAS and BRAF — required status

Required statusRAS and BRAF wild‑type required for specified colorectal/appendiceal indications

Context of requirementApplied when pertuzumab + trastuzumab is used as subsequent or initial therapy for HER2‑amplified colorectal/appendiceal disease

Relation to MMR/MSIRAS/BRAF wild‑type requirement appears alongside pMMR/MSS or dMMR/MSI‑H sequencing conditions in the colorectal criteria

MMR / MSI — biomarker references

MMR/MSI rolePolicy references pMMR/MSS and dMMR/MSI‑H status in colorectal/appendiceal treatment pathways

When requiredpMMR/MSS required for some initial/subsequent uses; dMMR/MSI‑H appears in contexts of ineligibility/progression on checkpoint inhibitor therapy

Combined biomarker logicMMR/MSI status is used with HER2‑amplification and RAS/BRAF status to determine eligibility in colorectal scenarios

Clearly state the primary diagnosis (e.g., HER2+ breast cancer, biliary tract cancer, colon/rectal/appendiceal carcinoma, salivary gland tumor) and treatment intent (neoadjuvant, adjuvant, first-line metastatic, subsequent line, etc.).

Documentation Required

Required Clinical Documentation

Clinical documentation submitted with the request must include tumor HER2 test results, diagnosis, treatment intent, prior therapy history (including prior anti-HER2 agents and timing), and the complete regimen composition showing pertuzumab will be given with trastuzumab (or trastuzumab biosimilar) and any cytotoxic agent as indicated.

HER2 testing method and result (IHC 3+ or ISH positive).
Primary diagnosis and stage (e.g., early stage, locally advanced, metastatic).
Treatment intent (neoadjuvant, adjuvant, first-line metastatic, subsequent line).
Prior systemic therapies and dates (especially prior trastuzumab or other HER2 inhibitors).
Regimen composition: pertuzumab must be prescribed with trastuzumab (or biosimilar) and specify the taxane or cytotoxic agent when required (docetaxel or paclitaxel; or vinorelbine/taxane as applicable).
Planned duration or number of cycles (e.g., maximum 18 cycles / 12 months where applicable).

Billing Rule

Combination Therapy Requirement

Pertuzumab must be used in combination with trastuzumab (or trastuzumab biosimilars) for the listed HER2-positive indications. For metastatic breast cancer first-line use, pertuzumab is required to be given with trastuzumab (or biosimilars) and either docetaxel or paclitaxel. For other settings (e.g., disease progression after trastuzumab-based therapy), pertuzumab may be used in combination with trastuzumab with or without a cytotoxic agent.

Combination with trastuzumab (or trastuzumab biosimilars) is mandatory — pertuzumab given without trastuzumab or after trastuzumab has been discontinued is a denial trigger.
First-line metastatic breast cancer: pertuzumab + trastuzumab (or biosimilar) + docetaxel or paclitaxel.
Disease progression after trastuzumab without prior pertuzumab: pertuzumab may be added in combination with trastuzumab, with or without cytotoxic therapy (e.g., vinorelbine or taxane).

Step Therapy

Sequencing / Step Therapy Notes

Provide prior therapy sequencing and timing in the clinical history. Specific sequencing rules apply for certain tumor types and settings and will affect authorization decisions.

Metastatic breast cancer first-line: no prior anti-HER2 therapy or chemotherapy for metastatic disease to qualify for first-line pertuzumab + trastuzumab + taxane.
Pertuzumab may be authorized as subsequent therapy in individuals previously treated with chemotherapy and trastuzumab (without prior pertuzumab) for one additional line of therapy in appropriate settings.
Colorectal/appendiceal cancer: when used as initial systemic therapy in combination with trastuzumab, prior FOLFOX or CapeOX within the past 12 months may be required for certain unresectable metachronous metastatic disease; sequencing rules also reference prior checkpoint inhibitor eligibility/progression and absence of prior HER2 inhibitor therapy as noted in criteria.

HER2 negativeIHC 0–1+ definitions or ISH negative numeric ranges (eg, singleprobe avg HER2 <4.0 signals/cell)

NCCN category 2A — explanation

NCCN category 2A meaningNCCN 2A indicates uniform NCCN consensus based on lower‑level evidence and is cited to support pertuzumab use in several tumor types in this policy

Policy usageNCCN 2A language is referenced for breast brain metastases, biliary tract, colorectal/appendiceal, and salivary gland indications

Implication for coveragePolicy incorporates NCCN 2A recommendations as part of the clinical criteria for approval where specified

Document status updated to Revised and clinical criteria provided for Perjeta and biosimilar Poherdy, including clarification of NCCN 2A recommendations and coding updates to include Poherdy mapping to HCPCS NOC/J‑codes.