Neighborhood Health Plan RI trastuzumab coverage update

Coverage Criteria

HER2-Positive Breast Cancer

Covered when ALL of the following are met for HER2-positive breast cancer:

Eligibility: Member has HER2-positive breast cancer meeting one of the following: (1) node-positive and/or tumor stage ≥ T2, OR (2) node-negative (N0) and tumor stage T1.

Supports neoadjuvant or adjuvant use

Neoadjuvant/Adjuvant acceptable regimens: Trastuzumab/trastuzumab biosimilar with or without Perjeta (pertuzumab) when given with one of the following chemotherapy backbones: paclitaxel following AC (doxorubicin + cyclophosphamide); docetaxel following AC (doxorubicin + cyclophosphamide); docetaxel or paclitaxel; TCH (docetaxel, carboplatin, and trastuzumab/trastuzumab biosimilar).

These regimens are acceptable for neoadjuvant or adjuvant therapy

Additional adjuvant/continuation options: Trastuzumab/trastuzumab biosimilar with docetaxel + cyclophosphamide, or continuation of trastuzumab/trastuzumab biosimilar ± pertuzumab as part of completed neoadjuvant/adjuvant therapy.

Metastatic/recurrent disease use: Trastuzumab/trastuzumab biosimilar with or without Perjeta (pertuzumab) for recurrent or metastatic HER2-positive breast cancer when used as first-line or subsequent therapy in one of the following ways: combined with tamoxifen, fulvestrant, or an aromatase inhibitor if ER/PR positive; combined with pertuzumab + a taxane regardless of ER/PR status; combined with single-agent chemotherapies (e.g., vinorelbine); or combined with tucatinib + capecitabine for patients with brain metastases or after progression on prior anti-HER2 therapy.

Supports first-line and subsequent-line metastatic use per listed combinations

HER2-Positive Gastric/Esophageal/GEJ Cancer

Covered when ALL of the following are met for HER2-positive gastric/esophageal/GEJ cancers:

Eligibility: Member has recurrent/metastatic gastric, esophageal, or esophagogastric junction (GEJ) adenocarcinoma that is HER2-positive (defined as IHC 3+ or FISH/ISH positive).

Regimen: Trastuzumab/trastuzumab biosimilar is being used in combination with cisplatin or oxaliplatin and 5-fluorouracil (or capecitabine), with or without pembrolizumab (Keytruda), as first-line therapy for recurrent/metastatic disease.

Use of trastuzumab or trastuzumab biosimilars is excluded for gastric or gastroesophageal junction (GEJ) adenocarcinoma after disease progression on a first‑line regimen that contained trastuzumab. Continuation of trastuzumab/trastuzumab biosimilar after documented disease progression on trastuzumab‑based therapy in HER2‑positive esophageal, gastroesophageal, or gastric adenocarcinomas is not covered.

Requests to use these agents for off‑label indications are considered investigational and not medically necessary unless supported by sufficient evidence from CMS‑recognized compendia or acceptable peer‑reviewed literature; abstracts, meeting‑only reports, and case reports without adequate supporting data are insufficient.

Requests will be excluded if dosing for trastuzumab/trastuzumab biosimilars, Phesgo, or pertuzumab exceeds the stated single‑dose limits. The single‑dose maximums are: for trastuzumab given every 3 weeks, 8 mg/kg loading and 6 mg/kg subsequent; for weekly trastuzumab, 4 mg/kg loading and 2 mg/kg subsequent; for Phesgo (pertuzumab/trastuzumab/hyaluronidase), 1,200 mg initial and 600 mg subsequent; and for pertuzumab (Perjeta), 840 mg initial and 420 mg every 3 weeks.

Total treatment duration for non‑metastatic HER2‑positive breast cancer with trastuzumab or trastuzumab biosimilars must not exceed 52 weeks (1 year; equivalent of 17 three‑week cycles). This maximum excludes any necessary, clinically indicated treatment interruptions such as perioperative recovery.

Use of trastuzumab, pertuzumab, Phesgo, or trastuzumab biosimilars for off‑label indications is considered investigational and not medically necessary unless the indication is supported by CMS‑recognized compendia or acceptable peer‑reviewed literature. Evaluations of supportive evidence should consider whether the patient and regimen are adequately represented in the published data and whether reported outcomes are clinically meaningful; meeting abstracts and case reports alone do not provide sufficient evidence.

Regimen
Trastuzumab/trastuzumab biosimilar +/- Perjeta (pertuzumab) with paclitaxel following AC (doxorubicin + cyclophosphamide)
Trastuzumab/trastuzumab biosimilar +/- Perjeta (pertuzumab) with docetaxel following AC (doxorubicin + cyclophosphamide)
Trastuzumab/trastuzumab biosimilar +/- Perjeta (pertuzumab) with docetaxel or paclitaxel (docetaxel/paclitaxel)
TCH (docetaxel, carboplatin, and trastuzumab/trastuzumab biosimilar) +/- Perjeta (pertuzumab)
Trastuzumab/trastuzumab biosimilar with docetaxel and cyclophosphamide

Regimen
Trastuzumab/trastuzumab biosimilar +/- Perjeta (pertuzumab) with endocrine therapy (tamoxifen, fulvestrant, or an aromatase inhibitor) for ER/PR-positive disease
Trastuzumab/trastuzumab biosimilar in combination with Perjeta (pertuzumab) and a taxane (docetaxel or paclitaxel), regardless of ER/PR status
Trastuzumab/trastuzumab biosimilar in combination with other single-agent chemotherapies (e.g., vinorelbine)
Trastuzumab/trastuzumab biosimilar in combination with Tukysa (tucatinib) + Xeloda (capecitabine) for metastatic HER2-positive breast cancer with brain metastases or after progression on prior anti‑HER2 therapy

Regimen
Trastuzumab/trastuzumab biosimilar in combination with cisplatin or oxaliplatin and 5‑fluorouracil (or capecitabine) as first‑line therapy
Trastuzumab/trastuzumab biosimilar in combination with cisplatin or oxaliplatin and 5‑fluorouracil (or capecitabine) with Keytruda (pembrolizumab) as first‑line therapy

Coding and Dosing Limits

Listed HCPCS/J and Q codesHCPCS

J9306	Injection, pertuzumab, 1 mg
J9316	Injection, pertuzumab, trastuzumab, and hyaluronidase-zzxf, per 10 mg
J9355	Injection, trastuzumab, excludes biosimilar, 10 mg
J9356	Injection, trastuzumab, 10 mg and hyaluronidase-oysk
Q5112	Injection, trastuzumab-dttb, biosimilar, (ontruzant), 10 mg
Q5113	Injection, trastuzumab-pkrb, biosimilar, (herzuma), 10 mg
Q5114	Injection, trastuzumab-dkst, biosimilar, (ogivri), 10 mg
Q5116	Injection, trastuzumab-qyyp, biosimilar, (trazimera), 10 mg
Q5117	Injection, trastuzumab-anns, biosimilar, (kanjinti), 10 mg
Q5146	Injection, trastuzumab-strf (hercessi), biosimilar, 10 mg

Pertuzumab/Combination HCPCSHCPCS

J9306	Injection, pertuzumab, 1 mg
J9316	Injection, pertuzumab, trastuzumab, and hyaluronidase-zzxf, per 10 mg

inv-08: Maximum total non-metastatic treatment duration — ≤ 52 weeks (17 three-week cycles)

Maximum total non-metastatic treatment duration≤ 52 weeks (1 year; equivalent of 17 three-week cycles). Note: interruptions for necessary therapy (eg, surgery/recovery) are not counted toward this limit.

Applies toNon-metastatic HER2-positive breast cancer receiving trastuzumab or trastuzumab biosimilars

Exclusion actionRequests exceeding this total duration will be excluded/denied per policy

inv-09: Trastuzumab single-dose maximum (q3w)

Trastuzumab (q3w) single-dose maximum8 mg/kg loading dose; 6 mg/kg for subsequent doses given every 3 weeks

Related exclusion

Provider Actions & Requirements

Prior Authorization

Prior Authorization Requirement

Prior Authorization Required — Evolent processes all medication requests for these agents. Requests must meet guideline-supported indications and include required supporting documentation (FDA labeling, CMS compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature). Continuation requests may be exempt when the member has not progressed, the prior authorization was active within the last year with no lapse >30 days, and no additional medications are being added.

All medication requests for trastuzumab products, pertuzumab, and Phesgo must be submitted to Evolent for prior authorization.
Continuation requests meeting the exemption criteria above do not require a new authorization review.

Note

Regimen Requirements

Acceptable chemotherapy regimens when trastuzumab/trastuzumab biosimilar ± pertuzumab are used as neoadjuvant or adjuvant therapy for HER2‑positive breast cancer. These regimens are enumerated and must be followed; this is not a step‑therapy sequence but a list of acceptable combinations.

Trastuzumab/trastuzumab biosimilar ± pertuzumab with paclitaxel following AC (doxorubicin + cyclophosphamide).

Line of Therapy

first-line | subsequent

Use allowed by line of therapy as follows:

Neoadjuvant/Adjuvant: Trastuzumab/trastuzumab biosimilar ± pertuzumab permitted in neoadjuvant or adjuvant settings for eligible early‑stage HER2‑positive breast cancer when given with the specified chemotherapy backbones.

Specific acceptable chemo combinations are listed in the HER2‑Positive Breast Cancer criteria

First-line metastatic: Trastuzumab/trastuzumab biosimilar combinations with chemotherapy (and pertuzumab + taxane regimens) are allowed as first‑line therapy for recurrent/metastatic HER2‑positive breast cancer; for gastric/GEJ/esophageal cancers trastuzumab with platinum + fluoropyrimidine (± pembrolizumab) is allowed first‑line when HER2‑positive.

Subsequent lines: Trastuzumab/trastuzumab biosimilar may be used in subsequent lines for metastatic HER2‑positive breast cancer per listed combinations (eg endocrine therapy combinations if ER/PR+, single‑agent chemotherapy, tucatinib + capecitabine for brain metastases or after prior anti‑HER2 progression).

Biomarker Requirements

inv-20: HER2 (IHC/FISH/ISH) — required testing: IHC 3+ or FISH/ISH positive

HER2-positive definition (IHC/FISH/ISH)IHC 3+ OR FISH/ISH positive

Required for gastric/GEJ/esophageal cancersDocumented HER2 positivity (IHC 3+ or FISH/ISH positive) is required to qualify for trastuzumab with platinum+fluoropyrimidine first-line

Testing methodsHER2 status must be determined by IHC or FISH/ISH as specified

inv-18: HER2-positive definition for gastric/GEJ — IHC 3+ or FISH/ISH positive

HER2-positive (gastric/GEJ) definitionIHC 3+ OR FISH/ISH positive

Coverage implicationRequired to meet eligibility for first-line trastuzumab-containing regimens in recurrent/metastatic gastric, esophageal, or GEJ adenocarcinoma

Background

Trastuzumab and pertuzumab are HER2‑directed monoclonal antibody therapies used across disease settings for HER2‑positive malignancies. In breast cancer, trastuzumab (with or without pertuzumab) is an established neoadjuvant, adjuvant, and metastatic treatment option when combined with recommended chemotherapy backbones or endocrine therapy as appropriate. For metastatic disease, pertuzumab plus a taxane is an accepted first‑line regimen and trastuzumab‑containing combinations are used in subsequent lines per guideline recommendations.

In HER2‑positive gastric, esophageal, and gastroesophageal junction (GEJ) adenocarcinomas, trastuzumab (with or without pembrolizumab) in combination with a platinum and fluoropyrimidine backbone is an accepted first‑line therapy for recurrent/metastatic disease when HER2 positivity is documented (IHC 3+ or FISH/ISH positive). Use and continuation decisions must align with FDA labeling, CMS‑recognized compendia, and major oncology guideline recommendations.

Revision History

2025-04converted_and_scope_expandedLatest

Converted to the new Evolent guideline template, replaced prior UM ONC_1134 guideline, and expanded the breast cancer indication to allow T1, N0 stage to receive trastuzumab/trastuzumab biosimilar +/- pertuzumab regimens.

2024-06added_biosimilar

Added the biosimilar Hercessi (trastuzumab-strf) to the guideline and updated references/administrative verbiage.

OpenPayer

Trastuzumab Products, Pertuzumab, and Phesgo — Coverage Criteria