Aetna bevacizumab Coverage & Prior Auth Update

Initial and continuation therapy

Aetna considers bevacizumab and listed biosimilars medically necessary for the following non-ocular indications (Initial Approval):

Medically necessary indications list: Includes: Ampullary adenocarcinoma (intestinal-type progressive, unresectable, or metastatic); recurrent or metastatic breast cancer; specified CNS cancers (glioma WHO grade 1, diffuse high-grade gliomas, glioblastoma, intracranial and spinal ependymoma excluding subependymoma, IDH‑mutant astrocytoma WHO grade 2–4, oligodendroglioma WHO grade 2–3, medulloblastoma, primary CNS lymphoma, meningiomas, limited and extensive brain metastases, and metastatic spine tumors); persistent, recurrent, or metastatic cervical or vaginal cancer; colorectal cancer including appendiceal and anal adenocarcinoma; unresectable or metastatic hepatocellular carcinoma when used as initial treatment in combination with atezolizumab; malignant pleural, peritoneal, pericardial, or tunica vaginalis testis mesothelioma per regimen criteria; recurrent/unresectable/advanced/metastatic non‑squamous NSCLC; epithelial ovarian, fallopian tube, or primary peritoneal cancer (including specified platinum‑sensitive and -resistant settings); relapsed or stage IV renal cell carcinoma; small bowel adenocarcinoma; selected soft tissue sarcomas (angiosarcoma single‑agent; solitary fibrous tumor/hemangiopericytoma with temozolomide); progressive/advanced/recurrent/metastatic uterine neoplasms/endometrial carcinoma; and unresectable locally advanced/recurrent/metastatic vulvar carcinoma (squamous and adenocarcinoma).

See Dosage and Administration section for indication‑specific dosing (e.g., 15 mg/kg q3w for many regimens; recurrent glioblastoma 10 mg/kg q2w).

Continuation of therapy: Continuation (reauthorization) is medically necessary when there is no unacceptable toxicity or disease progression while on the current bevacizumab‑containing regimen for a listed indication.

Document absence of progression and unacceptable toxicity per prior‑authorization requirements.

Experimental and investigational (not medically necessary)

Aetna considers bevacizumab and biosimilars experimental and investigational for the following non-ocular indications and combinations:

Experimental/Investigational indications: Includes (not all‑inclusive): acoustic neuroma; adrenocortical carcinoma; apocrine adenocarcinoma; bladder cancer; brain arteriovenous malformations; cancer of unknown primary (except trial‑specified regimens); carcinoid tumors; cholangiocarcinoma; Coat's disease; desmoid tumor; desmoplastic small round blue cell tumor; diffuse leptomeningeal glio‑neuronal tumor; esophageal cancer; gallbladder cancer; gastric and gastroesophageal junction adenocarcinoma; gastrointestinal stromal tumor (GIST); hemangioblastoma; hereditary hemorrhagic telangiectasia (HHT) and HHT‑related epistaxis (topical formulations not recommended); hydatidiform mole; islet cell cancer; laryngeal/respiratory papillomatosis (investigational/in case‑by‑case systemic use); melanoma; meningeal melanoma metastases; mucoepidermoid carcinoma of salivary gland; multiple myeloma; neuroendocrine tumors; neurofibromatosis; olfactory neuroblastoma; pancreatic cancer; pelvic bone cancer; pineal gland malignancy; prostate cancer; pseudomyxoma peritonei; radiation‑induced myelopathy; radiation necrosis (limited evidence contexts); respiratory papillomatosis; many sarcoma subtypes other than angiosarcoma/solitary fibrous tumor/hemangiopericytoma; squamous cell carcinoma of head and neck; small‑cell lung cancer; urothelial carcinoma; uveal ciliary melanocytoma; von Hippel‑Lindau disease, and others as listed in policy.

See full Experimental and Investigational list in policy.

Experimental combinations: Bevacizumab in combination with cetuximab or panitumumab; bevacizumab plus atezolizumab for RCC (outside specified trial‑driven criteria); and bevacizumab plus pemetrexed as maintenance for non‑squamous NSCLC are considered experimental/investigational.

FDA-Approved Indications

Covered when meeting FDA-approved indication and regimen-specific conditions

FDA-approved oncology indications: Bevacizumab (or listed biosimilars) is covered when used for FDA‑approved indications and regimens: metastatic colorectal cancer (with IV fluorouracil‑based chemotherapy for first‑ or second‑line; includes second‑line after progression on a bevacizumab‑containing regimen); first‑line unresectable/locally advanced/recurrent/metastatic non‑squamous NSCLC with carboplatin + paclitaxel (15 mg/kg q3w); recurrent glioblastoma in adults (single‑agent per label; recurrent dosing examples include 10 mg/kg q2w); metastatic renal cell carcinoma in combination with interferon alfa (dosing per label); persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel + cisplatin or paclitaxel + topotecan (GOG‑240 dosing 15 mg/kg q3w); and epithelial ovarian/fallopian tube/primary peritoneal cancer in specified platinum‑sensitive and ‑resistant settings and in stage III/IV post‑resection maintenance regimens as described in labeling.

Document indication, combination chemotherapy agents, line of therapy, and prior bevacizumab exposure when applicable.

Compendial / Off-label Uses

Compendial (off-label) uses may be considered with supporting evidence

Compendial/clinical‑trial uses: Coverage may be considered for compendial or trial‑supported off‑label uses when supported by authoritative compendia or clinical evidence and documented rationale. Examples include select CNS tumors (various gliomas, medulloblastoma, primary CNS lymphoma, meningioma), angiosarcoma, solitary fibrous tumor/hemangiopericytoma, ovarian cancer contexts beyond label, small bowel/appendiceal/ampullary/anal adenocarcinomas, mesothelioma subtypes per MAPS criteria, metastatic spine tumors, and cancer of unknown primary when used per published phase II regimen—coverage decisions require prior authorization and supporting documentation.

Local prior‑authorization policies may require compendia citation and trial data.

Evidence limitations and alert

Clinical evidence and limitations

Negative or limited evidence settings: Certain indications have limited, mixed, or negative evidence (e.g., adrenocortical carcinoma salvage regimen showed no activity; breast cancer follow‑up trials did not demonstrate meaningful survival benefit leading to regulatory removal of the advanced‑breast indication; pancreatic cancer phase III trials failed to show OS benefit). Use in these settings requires explicit supporting rationale and may be considered non‑covered depending on evidence and policy interpretation.

Submit trial data and prior therapy documentation when coverage is requested in these contexts.

Cervical cancer (recurrent/persistent/metastatic)

Covered when supported by randomized trial evidence demonstrating clinical benefit in the specified setting

Trial-supported indications: Bevacizumab is covered for recurrent, persistent, or metastatic cervical cancer when given in combination with platinum‑based chemotherapy per GOG‑240 (bevacizumab 15 mg/kg q3w) which demonstrated improved overall survival and higher response rates versus chemotherapy alone.

Document regimen, dosing, and eligibility consistent with trial population.

Colorectal cancer (metastatic)

Covered when used in metastatic colorectal cancer in combination with fluoropyrimidine-based chemotherapy in the first-line metastatic setting

Metastatic colorectal cancer first-line: Bevacizumab in combination with fluoropyrimidine‑based chemotherapy is covered for first‑line metastatic colorectal cancer based on randomized trials demonstrating an approximate 5‑month OS extension when added to IFL or similar regimens; includes appropriate second‑line fluoropyrimidine‑based combinations after progression on first‑line bevacizumab‑containing therapy.

Document chemotherapy backbone, line of therapy, and prior bevacizumab exposure if applicable.

Gliomas / glioblastoma (progressive or recurrent)

Covered when used for progressive glioblastoma or selected recurrent gliomas with supportive evidence

Recurrent glioblastoma/gliomas: Bevacizumab is covered for recurrent glioblastoma and select recurrent high‑grade gliomas after progression on standard therapy, based on phase II/registrational data showing radiographic responses and PFS benefit; FDA approval exists for recurrent glioblastoma in adults.

Document prior standard therapy and rationale for recurrent‑setting use; dosing examples include 10 mg/kg q2w for recurrent disease.

Investigational / limited evidence indications

Other tumor types with limited or investigational evidence — coverage may be considered in specific situations or clinical trials

Cancer of unknown primary (CUP): Phase II evidence suggests activity of bevacizumab‑containing empiric regimens (e.g., paclitaxel + carboplatin + bevacizumab + erlotinib induction then maintenance) in selected CUP patients; coverage may be considered on a case‑by‑case basis or within trials when no treatable subset is identified.

Document lack of identifiable treatable primary and rationale for empiric regimen.

Desmoplastic small round cell tumor (DSRCT): Evidence limited to case reports and small series; routine coverage not supported—consider only in clinical trials or exceptional circumstances with documentation.

Gastric/GEJ and other limited evidence tumors: Phase II data show activity in gastric/GEJ adenocarcinoma and other tumor types, but phase III confirmation is lacking; consider only with compelling evidence or trial enrollment.

Glioma / Recurrent glioblastoma

Covered when supported by clinical evidence and appropriate prior therapy documentation:

Recurrent Glioma (including glioblastoma): Bevacizumab may be considered for recurrent high‑grade gliomas after progression on standard therapy; pivotal trials report radiographic responses and improved PFS in the recurrent setting and the drug is FDA‑approved for progressive glioblastoma after standard therapy.

Document prior therapies and performance status; weight‑based dosing per label (e.g., 10 mg/kg q2w).

Newly diagnosed glioblastoma (first-line)

Use as adjunct to first-line radiotherapy/temozolomide:

Newly diagnosed glioblastoma (first-line adjunct): Addition of bevacizumab to radiotherapy plus temozolomide prolongs PFS but does not improve OS and is associated with higher rates of grade ≥3 adverse events and worse long‑term symptom burden in some studies; coverage for first‑line adjunct use requires careful justification and is generally not supported for OS‑driven indications.

Consider only when specific clinical rationale documented due to lack of OS benefit.

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC):

Advanced/unresectable HCC: Bevacizumab in combination with atezolizumab is indicated and covered for unresectable or metastatic HCC as initial systemic therapy per FDA approval; single‑agent or other combinations (eg, with erlotinib) have phase II evidence but notable bleeding risks and require careful patient selection.

Assess bleeding risk (varices), liver function, and performance status; document use as first‑line combination with atezolizumab per label.

HHT with refractory bleeding or hepatic involvement

Hereditary hemorrhagic telangiectasia (HHT) / severe bleeding:

Severe HHT‑related bleeding or high‑output cardiac failure: Systemic IV bevacizumab may be considered for patients with HHT who have chronic, refractory epistaxis or GI bleeding and/or high‑output cardiac failure after failure of conventional/local therapies. Initial courses commonly consist of 4–6 infusions of 5 mg/kg every 2–3 weeks with individualized maintenance; documented reductions in transfusion requirements and improved hemoglobin and epistaxis severity have been reported.

Topical/intranasal bevacizumab is not recommended based on RCTs; monitor BP, renal function, urine protein, and wound healing; document prior local therapies and transfusion history.

Hemangioblastoma / Radiation necrosis

Rare benign CNS tumors / radiation necrosis:

Hemangioblastoma and radiation necrosis: Case reports and small series suggest bevacizumab can stabilize hemangioblastoma growth and improve radiographic/clinical measures and steroid dependence in radiation necrosis; evidence is limited and use should be individualized with documentation of radiologic confirmation and prior steroid failure for RN.

Consider when surgery/radiation not feasible; document imaging, prior treatments, and planned follow‑up.

HHT (systemic bevacizumab)

Covered when ALL of the following are met (examples extracted from evidence context)

HHT - systemic bevacizumab example: Patient has hereditary hemorrhagic telangiectasia with chronic bleeding refractory to conventional/local therapies (epistaxis or GI bleeding) AND documentation of anemia or transfusion dependence where bevacizumab is intended to reduce bleeding/transfusion need.

Initial course commonly 4–6 infusions of 5 mg/kg every 2–3 weeks; maintenance individualized; monitor for hypertension and wound healing complications.

Malignant pleural mesothelioma (bevacizumab + pemetrexed-cisplatin)

Covered when ALL of the following are met

Malignant pleural mesothelioma - combination therapy: Patient has unresectable malignant pleural mesothelioma (or extrapolated malignant peritoneal mesothelioma) AND bevacizumab is given in combination with pemetrexed and cisplatin (or carboplatin) as per the MAPS trial selection criteria.

Patient selection should exclude poorly controlled hypertension, recent DVT, recent surgery/viscus perforation, and require adequate performance status (eg, ECOG 0–2).

Leiomyosarcoma (uLMS) — negative trial

Not supported / Not improved

Uterine leiomyosarcoma: Addition of bevacizumab to gemcitabine‑docetaxel did not improve PFS, OS, or ORR in first‑line metastatic uterine leiomyosarcoma (trial stopped for futility); routine use is not supported.

Gemcitabine‑docetaxel remains the standard of care in this setting.

Topical bevacizumab for HHT epistaxis

Evidence summary / investigational or not recommended contexts

Topical/intra‑nasal bevacizumab for HHT-related epistaxis: Multiple randomized trials failed to show topical intranasal bevacizumab more effective than saline or moisturizers; topical bevacizumab is not recommended. Submucosal injection or systemic IV approaches show promise but require further study.

Topical use not supported; systemic/submucosal use considered investigational/limited evidence.

Mesothelioma — First-line combination

Covered when ALL of the following are met for malignant pleural mesothelioma (extrapolated to peritoneal):

MAPS‑based coverage: Patient has unresectable malignant pleural mesothelioma (or extrapolated malignant peritoneal mesothelioma) AND bevacizumab is used in combination with pemetrexed plus platinum chemotherapy as first‑line therapy per MAPS trial regimens.

MAPS trial eligibility: age 18–75, ECOG 0–2, no substantial cardiovascular comorbidity; monitor for hypertension and thrombotic events.

Non-small cell lung cancer — First-line

Covered when ALL of the following are met for non-small cell lung cancer:

NSCLC first‑line coverage: Patient has unresectable, locally advanced, recurrent or metastatic non‑squamous NSCLC AND bevacizumab is administered with carboplatin and paclitaxel as initial systemic therapy (per FDA‑approved regimen).

Trials excluded squamous histology and patients with prior frank hemoptysis; document histology and absence of contraindications.

Multiple myeloma — insufficient benefit

Not routinely covered/considered investigational when evidence does not show benefit:

Multiple myeloma: Addition of bevacizumab to bortezomib in relapsed/refractory multiple myeloma did not show significant improvement in PFS or response rates in a phase II trial; routine use is not supported.

Use limited to clinical trials or exceptional circumstances with supporting data.

NETs and rare tumors — investigational/individualized

Considered investigational/under evaluation or for clinical trial use:

Neuroendocrine tumors: Bevacizumab has shown preliminary activity in NETs (eg, combinations with IFN or mTOR inhibitors) but evidence is insufficient for routine coverage; consider only in trials or with compelling documentation.

Separate considerations for pancreatic NET versus other NETs; further phase III data needed.

Olfactory neuroblastoma: Evidence limited to case reports and small series; routine coverage not supported—use individualized or investigational.

Neurofibromatosis type 2 — select use

May be considered for symptomatic benefit in selected patients with NF2-associated vestibular schwannomas when criteria are met:

NF2 vestibular schwannoma: Patient has neurofibromatosis type 2 with progressive vestibular schwannoma not amenable to standard therapy AND the treatment goal is hearing preservation or tumor volume reduction; bevacizumab dosing strategies reported include induction and maintenance schedules (eg, 7.5–10 mg/kg q2–3w) with hearing response rates ~35–41% in adults.

Document baseline hearing, growth pattern, prior interventions, and monitoring plan.

Approved Indication (Metastatic Renal Cell Carcinoma)

Covered when ALL of the following are met for FDA‑approved indication (example provided):

Metastatic RCC with interferon: Use of bevacizumab in combination with interferon alfa for metastatic renal cell carcinoma is covered when administered per FDA‑approved regimen and dosing, with documentation of indication and prior therapy as appropriate.

Dosing examples include 10 mg/kg q2w with interferon per trials.

Investigational / Not Medically Necessary

Not covered / investigational when evidence does not show clinically meaningful benefit:

Pancreatic adenocarcinoma: Bevacizumab for advanced pancreatic adenocarcinoma is considered investigational; phase III trials did not demonstrate OS benefit despite PFS improvements and TEC concluded it does not meet criteria for routine coverage.

References include Van Cutsem 2009 and TEC assessments.

Radiation Necrosis — Limited Evidence

Covered with criteria / experimental use considered when ALL apply (examples from limited evidence):

Radiation necrosis: Patient has symptomatic or radiographic radiation necrosis unresponsive to steroids AND documented radiologic confirmation of RN with prior steroid failure; proposed bevacizumab dosing and monitoring plan provided (reports commonly used 7.5 mg/kg q2w for ~4 cycles) and close radiographic follow‑up is required.

Evidence from small series and pooled analyses suggests radiographic and clinical improvement, but randomized data are limited.

RRP — Experimental / Case-by-case

Consider experimental or case-by-case coverage when ALL apply:

Recurrent respiratory papillomatosis (RRP): Severe, treatment‑refractory RRP (eg, >4 operations/year or airway compromise) AND prior surgical/interventional therapies documented AND plan for intralesional or systemic bevacizumab with objective response measures; systemic bevacizumab has shown prolonged surgical intervals in case series but evidence is limited to retrospective data.

Document frequency of prior procedures, airway compromise, and dosing/monitoring plan (eg, 15 mg/kg q3w with individualized taper in retrospective series).

Other Rare Indications — Insufficient Evidence

Insufficient evidence — investigational uses discussed in literature:

Pseudomyxoma peritonei (PMP): Case reports and small series suggest possible activity of bevacizumab alone or with chemotherapy in unresectable PMP, but evidence is inadequate for routine coverage; consider investigational use or clinical trial enrollment.

Olfactory neuroblastoma (ONB): Isolated case reports of palliation exist, but UpToDate does not list bevacizumab as a standard therapy; evidence insufficient for routine coverage.

Radiation‑induced myelopathy: Small case series report radiologic improvement but limited clinical benefit; considered investigational pending further study.

Investigational Combinations (Urothelial Cancer)

Coverage when used in clinical trials or supported regimens:

Urothelial carcinoma (investigational regimen): Bevacizumab combined with cisplatin and gemcitabine demonstrated high ORR in a phase II trial (ORR ~72%) but did not meet the predefined PFS improvement goal; use is investigational outside clinical trials and requires trial enrollment or strong justification.

Document ECOG performance status, trial eligibility criteria, and informed consent if investigational.

Respiratory papillomatosis (RRP) - evidence and contextual criteria

Context where systemic bevacizumab has been used for severe RRP

RRP candidate criteria: Severe RRP defined by high disease burden, frequent need for debridement, and/or tracheobronchial disease; prior surgical interventions documented and systemic bevacizumab dosing/monitoring plan in place (commonly 15 mg/kg q3w in reported adult series with individualized tapering after response).clinical judgment

Retrospective adult series reported reduced procedural frequency and prolonged intervals between surgeries.

Metastatic urothelial carcinoma — phase II context

Evidence for bevacizumab combined with cisplatin/gemcitabine (CGB)

CGB trial enrollment characteristics: Chemotherapy‑naive patients with metastatic or unresectable urothelial carcinoma and ECOG 0–1 received cisplatin + gemcitabine + bevacizumab (15 mg/kg q21d) in a phase II trial; ORR was 72% but the predefined PFS improvement goal was not met—use investigational outside trials.trial‑specific

Document trial‑like patient selection when used in investigational contexts.

Metastatic renal cell carcinoma — atezolizumab + bevacizumab

Phase III evidence for combination therapy compared with sunitinib

RCC PD‑L1+ population: In metastatic RCC, atezolizumab plus bevacizumab demonstrated improved investigator‑assessed PFS versus sunitinib in the PD‑L1 positive population (median PFS 11.2 vs 7.7 months; HR 0.74); OS benefit not established at interim analysis. Coverage of this combination is considered in PD‑L1+ patients aligned with trial criteria and documentation of PD‑L1 status.PD‑L1+

Document PD‑L1 assay results and rationale for PFS‑directed treatment.

Radiation necrosis (brain) — comparative and pooled evidence

Bevacizumab has been evaluated versus LITT and corticosteroids for radiation necrosis

RN response evidence: Multiple retrospective studies and small RCTs report radiographic and clinical improvement with bevacizumab for radiation necrosis, with meta‑analytic data showing similar symptomatic improvement and steroid weaning versus LITT but higher rates of partial radiographic regression at 6 months with bevacizumab; evidence remains limited and heterogeneous.study‑reported

Consider case‑by‑case coverage with required radiologic confirmation and documentation of prior steroid failure.

Trial-driven coverage considerations

Coverage considerations based on trial endpoints

mRCC - atezolizumab plus bevacizumab: Consider coverage in metastatic RCC patients with PD‑L1 positive tumors when the documented treatment goal is PFS improvement and PD‑L1 positivity is confirmed; OS benefit not yet established at interim analyses.PD‑L1+

Document PD‑L1 status and patient counseling regarding uncertainty of OS benefit.

NSCLC maintenance - bevacizumab plus pemetrexed: Combination maintenance with bevacizumab plus pemetrexed demonstrated PFS improvement without OS advantage and increased grade 3–4 toxicity; prefer pemetrexed alone for maintenance unless specific individualized rationale is documented.PFS benefit without OS improvement

Document rationale if combination maintenance selected despite lack of OS benefit.

Aetna considers bevacizumab (Avastin) and its biosimilars experimental and investigational for a broad set of non-ocular indications because effectiveness has not been established. The policy lists numerous specific tumor types and non-malignant conditions in this category, including but not limited to acoustic neuroma; adrenocortical carcinoma; bladder cancer; brain arteriovenous malformations; desmoid tumor; desmoplastic small round cell tumor; diffuse leptomeningeal glio-neuronal tumor; esophageal, gastric, and gallbladder cancers; gastrointestinal stromal tumors; hemangioblastoma; hereditary hemorrhagic telangiectasia (HHT) and HHT-related epistaxis; multiple myeloma; neuroendocrine tumors; olfactory neuroblastoma; pancreatic cancer; pseudomyxoma peritonei; radiation-induced myelopathy; radiation necrosis; respiratory papillomatosis; many sarcoma subtypes (except angiosarcoma, solitary fibrous tumor, and hemangiopericytoma); squamous cell carcinoma of the head and neck; small cell lung cancer; urothelial carcinoma; and von Hippel Lindau disease.

The policy also specifies certain experimental combinations: bevacizumab given concurrently with anti-EGFR antibodies (cetuximab or panitumumab), bevacizumab combined with atezolizumab for renal cell carcinoma, and bevacizumab combined with pemetrexed as maintenance therapy for non-squamous non-small cell lung cancer are all considered investigational due to insufficient evidence of safety and effectiveness.

Bevacizumab’s use in metastatic breast cancer was the subject of regulatory review after follow-up studies failed to confirm an overall survival benefit. The FDA granted an accelerated approval based on tumor growth slowing, but subsequent trials did not show meaningful survival extension and identified increased toxicity. An advisory committee voted in July 2010 to recommend removal of the advanced breast cancer indication, and the FDA subsequently moved to withdraw that indication based on lack of confirmed clinical benefit and higher rates of adverse effects.

A randomized adjuvant trial (mFOLFOX6 ± bevacizumab) did not demonstrate a sustained improvement in disease-free survival (DFS) for stage II/III colorectal cancer. Although a transient reduction in DFS events was observed during the year bevacizumab was administered, the overall DFS hazard ratio did not reach statistical significance (HR 0.89; 95% CI 0.76–1.04; p=0.15). Consequently, routine adjuvant use of bevacizumab with mFOLFOX6 in stage II/III colorectal cancer is not supported by the evidence and is not considered a benefit-providing indication.

OpenPayer

Bevacizumab for Non-Ocular Indications

Coverage Criteria