Mass General Brigham Health Plan angiogenesis inhibitors Prior Auth Update

Covered Indications and Criteria

General agent group eligibility

Authorization may be granted when ALL of the following are met for the listed agents:

group: Agent group: Alymsys (bevacizumab-maly), Avastin (bevacizumab), Mvasi (bevacizumab-awwb), Zirabev (bevacizumab-bvzr), Vegzelma (bevacizumab-adcd)

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Cervical Cancer

Covered when ALL of the following are met:

Cervical Cancer criteria: 1. Diagnosis of cervical cancer; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Requested agent will be used in combination with ONE of: a) paclitaxel + carboplatin (if PD-L1–positive tumors, pembrolizumab can be added), b) paclitaxel + cisplatin, c) paclitaxel + topotecan.

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Recurrent Glioblastoma and Selected Gynecologic Cancers

Covered when ALL of the following are met:

Recurrent glioblastoma / Ovarian / Fallopian / Primary peritoneal: 1. Diagnosis of ONE of the following: recurrent glioblastoma; ovarian cancer; fallopian cancer; primary peritoneal cancer; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required).

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Metastatic Colorectal Cancer

Covered when ALL of the following are met:

mCRC combination therapy: 1. Diagnosis of metastatic colorectal cancer (mCRC); 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Requested agent will be used in combination with ONE of: a) fluoropyrimidine-containing therapy; b) capecitabine-containing therapy; c) oxaliplatin-containing therapy; d) irinotecan-containing therapy.

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mCRC salvage with ramucirumab/aflibercept context: 1. Diagnosis of mCRC; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Requested agent will be used in combination with ONE of: a) FOLFIRI (irinotecan, leucovorin, 5-FU) or b) irinotecan; 5. Inadequate response, adverse reaction to ONE or contraindication to BOTH: a) 5-fluorouracil/leucovorin; b) capecitabine-based regimen.

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Metastatic Renal Cell Carcinoma

Covered when ALL of the following are met:

mRCC: 1. Diagnosis of metastatic renal cell carcinoma (mRCC); 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. If predominant clear cell histology, requested agent will be used in combination with interferon alfa.

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Non-Small Cell Lung Cancer (NSCLC) - multiple scenarios

Multiple NSCLC-related criteria sets (distinct disease presentations and lines):

Unresectable locally advanced/recurrent/metastatic non-squamous NSCLC: 1. Diagnosis of unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Requested agent will be used in combination with BOTH carboplatin and paclitaxel.

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EGFR mutation–positive non-squamous NSCLC: 1. Diagnosis of non-squamous NSCLC with EGFR mutation positive (e.g., exon 19 deletion or L858R); 2. Prescriber is an oncologist; 3. Requested agent will be used in combination with erlotinib.

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Advanced/metastatic adenocarcinoma or large cell NSCLC with PD-L1+: 1. Diagnosis of advanced or metastatic adenocarcinoma, large cell, NSCLC NOS with PD-L1 expression positive; 2. Prescriber is an oncologist; 3. Requested agent will be used in combination with ALL of: carboplatin, paclitaxel, and Tecentriq (atezolizumab) or Tecentriq Hybreza (atezolizumab + hyaluronidase).

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Hepatocellular Carcinoma (HCC)

HCC-related authorization criteria — multiple configurations present in document:

HCC with atezolizumab combination: 1. Diagnosis of unresectable or metastatic hepatocellular carcinoma (HCC); 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Requested agent will be used in combination with ONE of: a) Tecentriq (atezolizumab), b) Tecentriq Hybreza (atezolizumab + hyaluronidase).

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HCC with AFP >=400 ng/mL and prior therapy requirements: 1. Diagnosis of HCC; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Alpha fetoprotein (AFP) ≥400 ng/mL; 5. Inadequate response or adverse reaction to ONE or contraindication to ALL of: a) durvalumab +/- tremelimumab, b) lenvatinib, c) sorafenib, d) atezolizumab (+ bevacizumab).AFP >=400 ng/mL

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Ocular indications

Covered ocular indications when dosing meets specified regimen:

Ocular diseases (AMD, RVO, DME, DR, mCNV): 1. Diagnosis of ONE of: wet age-related macular degeneration (AMD); macular edema following retinal vein occlusion (RVO); diabetic macular edema (DME); diabetic retinopathy (DR); or myopic choroidal neovascularization (mCNV); 2. Requested dosing is 1.25 mg intravitreally every four or eight weeks or as needed.1.25 mg q4-8 weeks

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Gastric or GEJ Adenocarcinoma

Covered when ALL of the following are met:

Gastric/GEJ adenocarcinoma: 1. Diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Inadequate response or adverse reaction to ONE or contraindication to BOTH: a) fluoropyrimidine-containing chemotherapy regimen; b) platinum-containing chemotherapy regimen.

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Metastatic Colorectal Cancer (mCRC) - Initial Therapy

Covered when ALL of the following are met

mCRC main criteria: 1. Diagnosis of metastatic colorectal cancer; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Requested agent will be used in combination with ONE of: a) FOLFIRI (irinotecan, leucovorin, 5-FU) or b) irinotecan; 5. Inadequate response, adverse reaction to ONE or contraindication to BOTH: a) 5-fluorouracil/leucovorin; b) capecitabine-based regimen.

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Non-Small Cell Lung Cancer (NSCLC)

Covered when one of the following pathways is met

NSCLC pathways: Pathway A (both required): requested agent used with docetaxel AND inadequate response/adverse reaction/contraindication to a platinum-containing chemotherapy regimen. Pathway B (all required): requested agent used with erlotinib AND tumor displays EGFR exon 19 deletion or exon 21 L858R mutation. Pathway C: inadequate response or adverse reaction to OR contraindication to ALL of: osimertinib (Tagrisso), afatinib (Gilotrif), gefitinib (Iressa), dacomitinib (Vizimpro).

Includes EGFR-mutation driven option and prior therapy pathways

Zaltrap (ziv-aflibercept)

Covered when ALL of the following are met

Zaltrap criteria: 1. Diagnosis of metastatic colorectal cancer; 2. Prescriber is an oncologist; 3. Appropriate dosing (weight required); 4. Requested agent will be used in combination with irinotecan or FOLFIRI; 5. Inadequate response or adverse reaction to ONE of: CAPEOX, FOLFOX, a fluoropyrimidine (capecitabine or 5-FU), or oxaliplatin-based therapy OR contraindication to ALL of these regimens; 6. Inadequate response, adverse reaction, or contraindication to a bevacizumab product.

Step therapy requires prior oxaliplatin/fluoropyrimidine exposure and bevacizumab failure/contraindication

Continuation of Therapy

Continuation: Resubmission by prescriber will infer a positive response to therapy.

Used to support reauthorization requests (chunk 21)

Authorizations do not consider products obtained as samples or provided through a manufacturer's patient assistance program when performing case-by-case continuation reviews for members new to the plan. Documentation should reflect commercially obtained product and typical procurement pathways; lack of such documentation may affect the review outcome.

For Zaltrap (ziv‑aflibercept), coverage requires documented prior exposure and failure or intolerance to standard oxaliplatin/fluoropyrimidine regimens. Specifically, the request must show inadequate response, adverse reaction, or a contraindication to one of the listed regimens (CAPEOX, FOLFOX, a fluoropyrimidine such as capecitabine or 5‑FU, or other oxaliplatin‑based therapy). In addition, there must be documentation of inadequate response, adverse reaction, or contraindication to a bevacizumab product before Zaltrap will be approved.

Requests to use an angiogenesis inhibitor for NSCLC must meet one of the policy's specified pathways. Absent documentation that the agent will be used with docetaxel plus prior platinum‑regimen failure, or with erlotinib in a tumor harboring an EGFR exon 19 deletion or exon 21 L858R, or documentation of failure/contraindication to the listed EGFR TKIs, the request is considered not medically necessary. In practice this means the prescriber must supply the intended combination partner and prior therapy history (or biomarker results) consistent with one of the policy pathways; otherwise the request should be denied.

Permitted Combination Regimens

Cancer type / setting	Example covered regimen(s)	Coverage status
{"text":"Cervical cancer","status":""},{"text":"Paclitaxel + carboplatin (± pembrolizumab if PD‑L1 positive); paclitaxel + cisplatin; paclitaxel + topotecan","status":"covered"},{"text":"Covered when used in listed combinations per criteria","status":""}
{"text":"Non‑squamous NSCLC (unresectable/locally advanced/recurrent/metastatic)","status":""},{"text":"Carboplatin + paclitaxel (with bevacizumab products)","status":"covered"},{"text":"Covered when used in combination with both carboplatin and paclitaxel","status":""}
{"text":"Advanced/metastatic adenocarcinoma or large cell NSCLC with PD‑L1+","status":""},{"text":"Carboplatin + paclitaxel + atezolizumab (Tecentriq) or atezolizumab + hyaluronidase","status":"covered"},{"text":"Covered for PD‑L1 positive tumors in listed combination","status":""}
{"text":"Initial therapy NSCLC when PD‑1/PD‑L1 inhibitors contraindicated (PS 0‑2)","status":""},{"text":"Carboplatin + pemetrexed or cisplatin + pemetrexed (with bevacizumab products)","status":"covered"},{"text":"Covered as first‑line alternative when PD‑1/PD‑L1 contraindicated","status":""}
{"text":"NSCLC maintenance therapy (PS 0‑2)","status":""},{"text":"Bevacizumab product as monotherapy or combined with atezolizumab (± hyaluronidase) or pemetrexed; bevacizumab + atezolizumab may be continued without carboplatin/paclitaxel if responding","status":"covered"},{"text":"Covered per maintenance criteria","status":""}
{"text":"NSCLC second‑line / post‑platinum or EGFR contexts","status":""},{"text":"Bevacizumab product + docetaxel; bevacizumab product + erlotinib for EGFR exon19 or exon21 L858R mutations; other EGFR TKI failure pathways","status":"covered"},{"text":"Covered when meeting specified prior‑therapy or biomarker pathways","status":""}
{"text":"Hepatocellular carcinoma (HCC)","status":""},{"text":"Bevacizumab product + atezolizumab (Tecentriq) or atezolizumab + hyaluronidase","status":"covered"},{"text":"Covered in combination with atezolizumab per HCC criteria","status":""}
{"text":"Metastatic colorectal cancer (mCRC)","status":""},{"text":"FOLFIRI (irinotecan, leucovorin, 5‑FU) or irinotecan-containing regimens; bevacizumab products used with these regimens","status":"covered"},{"text":"Covered when used with FOLFIRI or irinotecan and prior regimen conditions met","status":""}

Regimen / prior regimen	Clinical context	Coverage status
{"text":"FOLFIRI (irinotecan + leucovorin + 5‑fluorouracil)","status":""},{"text":"Used in metastatic colorectal cancer as combination partner for angiogenesis inhibitors (salvage/second‑line contexts)","status":"covered"},{"text":"Covered when combined with requested agent and criteria met","status":""}
{"text":"Irinotecan (single agent or irinotecan‑containing regimens)","status":""},{"text":"Alternative combination for mCRC when used with angiogenesis inhibitors; applicable when prior fluoropyrimidine exposure noted","status":"covered"},{"text":"Covered per mCRC criteria","status":""}
{"text":"Docetaxel combinations","status":""},{"text":"NSCLC second‑line/post‑platinum setting: requested agent used with docetaxel after inadequate response/adverse reaction/contraindication to platinum chemotherapy","status":"covered"},{"text":"Covered when prior platinum failure documented and used with docetaxel","status":""}
{"text":"Erlotinib combinations","status":""},{"text":"NSCLC with EGFR exon 19 deletion or exon 21 L858R: requested agent used with erlotinib","status":"covered"},{"text":"Covered when EGFR sensitizing mutation documented","status":""}
{"text":"CAPEOX; FOLFOX; oxaliplatin‑based therapy; fluoropyrimidine (5‑FU or capecitabine)","status":""},{"text":"Prior regimens required (for Zaltrap): inadequate response/adverse reaction to ONE of these or contraindication to ALL before approving ziv‑aflibercept; these are common oxaliplatin/fluoropyrimidine therapies used in mCRC and gastric cancer","status":"covered"},{"text":"Required prior exposure/ failure documented for Zaltrap coverage","status":""}

Line of Therapy Specific Criteria

first-line | maintenance | second-line

Line of therapy options:

First-line (initial) NSCLC when PD-1/PD-L1 contraindicated: Use in first-line setting for advanced/metastatic NSCLC (PS 0-2) when PD-1/PD-L1 inhibitors are contraindicated; requested agent will be used with ONE of: carboplatin + pemetrexed OR cisplatin + pemetrexed.

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Maintenance NSCLC: Maintenance therapy following response/stable disease (PS 0-2): requested agent may be used as monotherapy OR in combination with atezolizumab (or atezolizumab + hyaluronidase) OR with pemetrexed. Note: bevacizumab plus atezolizumab can be continued without carboplatin and paclitaxel after response/stability.

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Second-line NSCLC (post-platinum or EGFR-directed): Second-line options include: agent with docetaxel after inadequate response/adverse reaction/contraindication to platinum-containing chemotherapy; OR agent with erlotinib for tumors with EGFR exon 19 deletion or exon 21 L858R; OR use after inadequate response/adverse reaction to listed EGFR TKIs (osimertinib, afatinib, gefitinib, dacomitinib).

Biomarker and Laboratory Requirements

PD-L1 / AFP / EGFR

PD-L1 expressionPD-L1 positive (no numeric threshold specified)

AFP thresholdAlpha fetoprotein (AFP) ≥400 ng/mL

EGFR mutation requirementEGFR exon 19 deletion or exon 21 L858R

EGFR exon 19 deletion or exon 21 L858R

Required EGFR mutationsEGFR exon 19 deletion or exon 21 L858R

Context of useRequired for use of the requested agent in combination with erlotinib in NSCLC

Supporting pathway

Authorization, Documentation, and Prior Therapy Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for medical-benefit use of the listed angiogenesis inhibitors. Authorization may be reviewed on a case-by-case basis for members who are new to the plan and currently receiving treatment with the requested medication; lack of documentation that the member is new to the plan and currently receiving treatment may affect case-by-case review. Providers must supply diagnosis, prescriber specialty (oncologist for oncology indications), and documentation of appropriate dosing (including patient weight).

Prior authorization required for listed angiogenesis inhibitors when billed to the medical benefit.
Case-by-case reviews possible for members new to plan who are currently receiving treatment; documentation must show member status and ongoing therapy.
Required documentation: diagnosis, oncologist prescriber for oncology indications, patient weight for dosing, and evidence of combination chemotherapy where applicable.

Documentation Required

mCRC Combination and Prescriber Requirements

Dosing and Key Code / Test Values

Intravitreous bevacizumab dosing for ocular indications

Intravitreal dose1.25 mg per injection

Dosing intervalEvery 4 or 8 weeks or as needed

IndicationsWet AMD, macular edema following RVO, diabetic macular edema (DME), diabetic retinopathy (DR), myopic choroidal neovascularization (mCNV)

Alpha fetoprotein (AFP)

AFP threshold (repeat)AFP ≥400 ng/mL

Use caseReferenced in HCC biomarker requirements for authorization

Prior therapy relation

Definitions and Biosimilar List

bevacizumab biosimilars

Biosimilars listedAlymsys (bevacizumab-maly); Mvasi (bevacizumab-awwb); Vegzelma (bevacizumab-adcd); Zirabev (bevacizumab-bvzr)

Equivalence statementThese products are biosimilars to reference bevacizumab (Avastin) and have largely the same FDA‑approved indications as Avastin (some indication differences for certain biosimilars noted)

Indication caveatAlymsys and some biosimilars may lack certain Avastin indications (e.g., some ovarian cancer and HCC approvals differ)

Platinum-based chemotherapy

DefinitionPlatinum-based chemotherapy regimens commonly include cisplatin, carboplatin, or oxaliplatin depending on tumor type

NSCLC examplesCisplatin and carboplatin are often used in NSCLC regimens

Background and Purpose

Angiogenesis inhibitors (e.g., bevacizumab and its biosimilars, ramucirumab, and ziv‑aflibercept) are monoclonal antibodies or fusion proteins that inhibit tumor neovascularization and are used across a range of advanced malignancies. These agents are typically given in combination with chemotherapy or immunotherapy for solid tumors (for example, colorectal cancer, non‑small cell lung cancer, hepatocellular carcinoma, and others). The policy aligns coverage pathways with standard oncology practice and guideline updates, and was revised to add agent‑specific criteria and to document off‑label intravitreal use of bevacizumab for certain ophthalmologic conditions.

Policy Changes and Review History

2025-09-01revised

Removed Child-Pugh class requirement for Avastin in HCC and updated Cyramza HCC and metastatic RCC criteria per NCCN; Tecentriq Hybreza added as combination option with bevacizumab products for HCC and NSCLC.

2024-10-01revised

NCCN-based update: NSCLC criteria for Cyramza were updated to include osimertinib or dacomitinib as trial options; cervical cancer regimens clarified to allow paclitaxel+carboplatin with addition of pembrolizumab if PD-L1 positive.

2023-02-08added

OpenPayer

Angiogenesis inhibitors (bevacizumab, biosimilars, ramucirumab, ziv-aflibercept)

Covered Indications and Criteria

Permitted Combination Regimens

Line of Therapy Specific Criteria

Biomarker and Laboratory Requirements

Authorization, Documentation, and Prior Therapy Requirements

Dosing and Key Code / Test Values

Definitions and Biosimilar List

Background and Purpose

Policy Changes and Review History