Description

Bevacizumab (Avastin®) is a humanized monoclonal antibody that produces angiogenesis inhibition by inhibiting vascular endothelial growth factor A (VEGF-A). VEGF-A is a chemical signal that stimulates angiogenesis in a variety of diseases, especially in cancer.

Criteria

Coverage is subject to the specific terms of the member’s benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Food and Drug Administration (FDA) Indications

Bevacizumab (Avastin) may be considered medically necessary for individuals who meet ANY ONE of the following criteria:

Cervical Cancer

• For the treatment of persistent, recurrent or metastatic cervical cancer in combination with ONE of the following:
  • Paclitaxel and cisplatin; or
  • Paclitaxel and topotecan; or

Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• For treatment in ANY of the following:
  • In combination with carboplatin and paclitaxel, followed by bevacizumab (Avastin) as a single agent, for stage III or IV disease following initial surgical resection; or
  • In combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for individuals with platinum-resistant recurrent disease who received no more than two (2) prior chemotherapy regimens; or
  • In combination with ANY of the following regimens, followed by bevacizumab (Avastin) as a single agent for platinum-sensitive recurrent disease:
    • In combination with carboplatin and paclitaxel; or
    • In combination with carboplatin and gemcitabine.

Glioblastoma

• For treatment of recurrent glioblastoma in adults; or

Metastatic Colorectal Cancer

• In combination with intravenous 5-fluorouracil-based chemotherapy for first or second-line treatment; or
• As second-line treatment in individuals who have progressed on a first-line bevacizumab (Avastin)-containing regimen in ONE of the following:
  • In combination with fluoropyrimidine-irinotecan; or
  • In combination with fluoropyrimidine-oxaliplatin; or

Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

• In combination with carboplatin and paclitaxel as first-line treatment of individuals with unresectable, locally advanced, recurrent or metastatic non-squamous cell type NSCLC; or

Renal Cell Carcinoma

• For treatment of metastatic renal cell carcinoma in combination with interferon alfa.

The use of bevacizumab (Avastin) for any other oncologic indication is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

National Comprehensive Cancer Network (NCCN) Recommendations

The use of bevacizumab (Avastin) may be considered medically necessary for the following conditions:

AIDS-Related Kaposi Sarcoma

• Subsequent systemic therapy given with antiretroviral therapy (ART) for relapsed/refractory advanced, cutaneous, oral, visceral, or nodal disease that has progressed on or not responded to first-line systemic therapy, and progressed on alternate first-line systemic therapy; or

Angiosarcoma

• As single agent therapy for angiosarcoma; or

Breast Cancer

• In combination with paclitaxel for recurrent or stage IV (M1) invasive breast cancer human epidermal growth factor receptor 2 (HER2)-negative disease in ANY of the following:
• • With symptomatic visceral disease or visceral crisis; or
  • That is hormone receptor-negative or hormone receptor-positive and endocrine therapy refractory; or

Central Nervous System (CNS) Cancers

• For the treatment of recurrent anaplastic gliomas as ANY of the following:
• • As a single agent; or
  • In combination with irinotecan, carmustine, lomustine, temozolomide, or carboplatin; or
• For the treatment of recurrent glioblastomas as ANY of the following:
  • As a single agent; or
  • In combination with carmustine, lomustine, temozolomide, or carboplatin; or
• As single-agent treatment for progression or recurrent disease, if received prior radiation therapy and ANY of the following:
  • Gross total or subtotal resection; or
  • Localized recurrence; or
  • Evidence of metastases in brain, spine, or cerebrospinal fluid (CSF); or
• As single agent treatment or in combination with everolimus for surgically inaccessible recurrent or progressive meningioma disease when radiation is not possible; or
• As short course single agent therapy for management of symptoms driven by radiation therapy necrosis, poorly controlled vasogenic edema, or mass effect for ANY of the following conditions:
  • Adult low-grade (WHO Grade II) infiltrative supratentorial astrocytoma/oligodendroglioma; or
  • Anaplastic gliomas; or
  • Glioblastoma; or
  • Adult intracranial and spinal ependymoma, excluding subependymoma; or
  • Adult medulloblastoma; or
  • Primary CNS lymphoma; or
  • Meningiomas; or
  • Limited brain metastases; or
  • Extensive brain metastases; or
  • Leptomeningeal metastases; or
  • Metastatic spine tumors; or

Cervical Cancer

• Used as first line therapy in combination with paclitaxel, cisplatin, carboplatin, or topotecan; or
• As a second line single agent therapy for:
  • Local/regional recurrence; or
  • Stage IVB or distant metastases; or

Colon Cancer

• Used in combination with capecitabine, or  FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), or CapeOX (capecitabine and oxaliplatin), FOLFOXIRI (fluoruracil, leucovorin, oxaliplatin, and irinotecan) or 5-FU/LV (fluorouracil and leucovorin) regimen for:
• • Primary treatment for locally unresectable or medically inoperable disease; or
  • Therapy for unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy; or
  • Primary treatment for synchronous abdominal/peritoneal metastases that are non-obstructing, or following local therapy for individuals with existing or imminent obstruction; or
  • Unresectable metachronous metastases of other sites; or
  • Primary treatment for unresectable metachronous metastases in individuals who have:
    • Not received previous adjuvant FOLFOX or CapeOX within the past 12 months; or
    • Received 5-FU/LV or capecitabine therapy; or
    • Have not received any previous chemotherapy; or
  • Unresectable metachronous metastases that remain unresectable after primary treatment ; or
• Primary treatment for unresectable synchronous liver and/or lung metastases in combination with ANY of the following:
  • FOLFOX; or
  • FOLFIRI; or
  • FOLFOXIRI; or
  • CapeOX; or
• Used in combination with FOLFOXIRI (fluorouracil, leucovorin, and irinotecan), or  FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or CapeOX (capecitabine and oxaliplatin) regimen, or  FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen as:
  • Perioperative therapy for resectable synchronous liver and/or lung metastases.
• As anti-angiogenic therapy as primary therapy for individuals with unresectable metachronous metastases and previous adjuvant FOLFOX or CapeOX within the past 12 months in combination with ANY of the following:
  • Irinotecan; or
  • FOLFIRI regimen; or
• Subsequent therapy after first progression of advanced or metastatic disease in ANY of the following:
  • As anti-angiogenic agent in combination with irinotecan or FOLFIRI regimen for disease previously treated with oxaliplatin-based therapy without irinotecan; or
  • In combination with FOLFOX or CapeOX regimen for disease previously treated with irinotecan-based therapy without oxaliplatin; or
  • In combination with irinotecan or FOLFIRI for individuals previously treated with fluoropyrimidine therapy without irinotecan or oxaliplatin; or
  • In combination with FOLFOX, CapeOX, or irinotecan and oxaliplatin for individuals previously treated with fluoropyrimidine therapy without irinotecan or oxaliplatin
• Therapy in combination with capecitabine or with FOLFOX, FOLFIRI, CapeOX, FOLFOXIRI or 5-FU/LV regimen:
  • As adjuvant treatment following synchronized or staged resection for synchronous liver and/or lung metastases that converted from unresectable to resectable disease; or
  • As adjuvant treatment (following resection and/or local therapy) for resectable metachronous metastases in individuals who have received previous chemotherapy or had growth on neoadjuvant chemotherapy; or
  • As adjuvant treatment for unresectable metachronous metastases that converted to resectable disease; or

Kidney Cancer

• As therapy for relapse or stage IV disease in ANY of the following:
• • In combination with interferon alfa-2b as first-line therapy for clear cell histology; or
  • As single-agent subsequent therapy for clear cell histology; or
  • As single-agent systemic therapy for non-clear cell histology; or
  • In combination with erlotinib for non-clear cell histology with advanced papillary renal cell carcinoma including hereditary leiomyomatosis and renal cell cancer (HLRCC); or
  • In combination with everolimus as systemic therapy for non-clear cell histology; or

Malignant Pleural Mesothelioma

• In combination with pemetrexed** and cisplatin or carboplatin followed by single-agent maintenance bevacizumab (Avastin) therapy as treatment of ANY of the following:
• • Unresectable clinical stage I-IIIA disease and tumors of epithelial, sarcomatoid, or mixed histology; or
  • Treatment of clinical stage IIIB or IV disease or medically inoperable tumors in individuals with performance status (PS) 0-2; or

Non-Small Cell Lung Cancer

• Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (greater than or equal to 50%) tumors that are EGFR, ALK negative or unknown and no contraindications to the addition of pembrolizumab or atezolizumab and performance status 0-2 in combination with atezolizumab, carboplatin, and paclitaxel for nonsquamous cell histology; or
• Treatment in combination with carboplatin and paclitaxel or pemetrexed (if contraindications to the addition of pembrolizumab or atezolizumab) or in combination with cisplatin and pemetrexed, or in combination with atezolizumab, carboplatin, and for recurrent, advanced or metastatic disease in individuals with performance status 0-1, tumors of nonsquamous cell histology, and no history of recent hemoptysis in ANY of the following:
  • As initial systemic therapy for EGFR, ALK, ROS1, BRAF negative or unknown, and PD-L1 less than 50% or unknown; or
  • First line or subsequent therapy for BRAF V600E-mutation positive tumors; or
  • Subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, osimertinib, or dacomitinib therapy; or
  • Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, alectinib, or brigatinib therapy; or
  • Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib or ceritinib therapy; or
  • Subsequent therapy for PD-L1 expression-positive (greater than or equal to 50%) tumors and EGFR, ALK negative or unknown and no prior platinum-doublet chemotherapy; or
• Continuation maintenance therapy for recurrent, advanced, or metastatic disease in individuals with performance status 0-2, tumors of nonsquamous cell histology, and no history of recent hemoptysis who achieve tumor response or stable disease following first-line chemotherapy in ANY of the following:
  • As a single agent; or
  • In combination with pemetrexed if previously used with a first-line pemetrexed/platinum chemotherapy regimen.; or
  • In combination with atezolizumab if previously used first-line as part of an atezolizumab carboplatin/paclitaxel/bevacizumab (Avastin) regimen; or

Ovarian Epithelial Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer

• As neoadjuvant chemotherapy in combination with paclitaxel and carboplatin for bulky stage III-IV disease or poor surgical candidates*; or
• Used in combination with paclitaxel and carboplatin in ANY of the following:
  • Primary treatment in individuals with incomplete previous surgery and/or staging with stage II-IV and suspected unresectable residual disease; or
  • Primary adjuvant therapy for pathologic stage II-IV disease; or
• As post-remission maintenance therapy as a single agent if used previously as part of a combination therapy for individuals with partial or complete remission following ANY of the following:
  • Primary therapy for stage II-IV disease; or
  • Recurrent therapy for platinum-sensitive disease; or
• In combination with paclitaxel and carboplatin for rising cancer antigen 125 (CA-125) levels or clinical relapse in individuals who have received no prior chemotherapy; or
• For persistent disease or recurrence in ANY of the following:
  • If platinum-sensitive, in combination with carboplatin and gemcitabine; or
  • If platinum-sensitive, in combination with carboplatin and paclitaxel; or
  • If platinum-resistant, in combination with liposomal doxorubicin, weekly paclitaxel, or topotecan; or
  • As a single agent; or

• As adjuvant treatment in combination with carboplatin and paclitaxel for pathologic stage I-IV malignant mixed Mullerian tumors carcinosarcoma disease; or
• As adjuvant treatment in combination with carboplatin and paclitaxel for pathologic stage II-IV clear cell carcinoma disease; or
• As adjuvant treatment for pathologic stage II-IV mucinous carcinoma disease in combination with ANY of the following:
  • Carboplatin and paclitaxel; or
  • FOLFOX; or
  • CapeOX; or
• As therapy for persistent mucinous carcinoma disease or recurrence in combination with ANY of the following:
  • FOLFOX; or
  • CapeOX; or

• As adjuvant treatment in combination with carboplatin and paclitaxel for pathologic stage II-IV low-grade serous/grade 1 endometrioid epithelial carcinoma or borderline epithelial tumors with invasive implants; or
• As single agent for clinical relapse in individuals with stage II-IV malignant sex cord-stromal tumor disease; or

Rectal Cancer

• Primary treatment for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable in combination with ANY ONE of the following:
  • FOLFIRI; or
  • FOLFOX; or
  • CapeOX; or
  • FOLFOXIRI; or
• Anti-angiogenic therapy as primary treatment for individuals with unresectable metachronous metastases and previous adjuvant FOLFOX or CapeOX within the past 12 months in combination with:
  • Irinotecan; or
  • FOLFIRI regimen;or
• Used in combination with capecitabine or with FOLFOX, FOLFIRI, CapeOX, or 5-FU/LV as:
  • Primary treatment for ANY ONE of the following:
    • T3, N Any disease; or
    • T1-2, N1-2 disease; or
    • T4, N Any disease; or
    • Locally unresectable or medically inoperable disease if resection is contraindicated following neoadjuvant therapy; or
  • For synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable with no progression of primary tumor after primary systemic therapy; or
  • Following short-course radiation therapy or chemoradiation for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable with progression of primary tumor after primary systemic therapy; or
  • As primary treatment for synchronous abdominal/peritoneal metastases that are non-obstructing, or following local therapy for individuals with existing or imminent obstruction; or
  • As primary treatment for synchronous unresectable metastases of other sites; or
  • Primary treatment for unresectable metachronous metastases in individuals for ANY of the following:
    • Who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months; or
    • Who have received previous 5-FU/LV or capecitabine treatment; or
    • Who have not received any previous chemotherapy; or
  • For unresectable metachronous metastases that remain unresectable after primary treatment; or
• As therapy in combination with capecitabine or with FOLFOX, FOLFIRI, CapeOX, FOLFOXIRI, or 5-FU/LV for:
  • Adjuvant treatment following resection and/or local therapy for resectable metachronous metastases in individuals who have received previous chemotherapy or had grown on neoadjuvant chemotherapy; or
  • Adjuvant treatment for unresectable metachronous metastases that converted to resectable disease after primary treatment; or
• Subsequent therapy after first progression for unresectable advanced or metastatic disease:
  • In combination with irinotecan or FOLFIRI for disease previously treated with oxaliplatin-based therapy without irinotecan; or
  • In combination with FOLFOX or CapeOX regimen for disease previously treated with irinotecan-based therapy without oxaliplatin; or
  • In combination with irinotecan or FOLFIRI if previously treated with fluoropyrimidine therapy without irinotecan or oxaliplatin; or
  • In combination with FOLFOX, CapeOX, or irinotecan and oxaliplatin if previously treated with fluoropyrimidine therapy without irinotecan or oxaliplatin;or

Soft Tissue Sarcoma: Solitary Fibrous Tumor/Hemangiopericytoma

• In combination with temozolomide for the treatment of solitary fibrous tumor and hemangiopericytoma; or 

Squamous Cell Carcinoma- Vulvar Cancer

• In combination with cisplatin and paclitaxel, or carboplatin and paclitaxel in ANY of the following:
  • As additional treatment for unresectable locally advanced disease clinically positive for residual tumor at the primary site and/or nodes; or
  • As additional treatment for locally advanced disease with positive margins following resection; or
  • As primary treatment for metastatic disease beyond the pelvis; or
  • For isolated groin/pelvic recurrence if prior external beam radiation therapy (EBRT); or
  • For clinical nodal or distant recurrence with multiple pelvic nodes, distant metastases, or prior pelvic EBRT; or

Uterine Neoplasms – Endometrial Carcinoma 

• Used in combination with carboplatin and paclitaxel for advanced and recurrent disease; or
• Single-agent therapy for disease that has progressed on prior cytotoxic chemotherapy.

The use of bevacizumab (Avastin) for any other oncologic indication listed above is considered experimental/investigational, and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

The use of bevacizumab-awwb (Mvasi) may be considered medically necessary when ANY of the following criteria are met for the following conditions:

Metastatic Colorectal Cancer

• As first or second-line treatment of individuals with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil-based chemotherapy; or
• As second-line treatment of individuals with metastatic colorectal cancer who have progressed on first-line bevacizumab product-containing regimen in combination with ONE of the following:
  • Fluoropyrimidine-irinotecan; or
  • Fluoropyrimidine-oxaliplatin; or

Non-Squamous Non-Small Cell Lung Cancer

• As first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer in combination with carboplatin and paclitaxel; or

Glioblastoma

• As treatment for glioblastoma with progressive disease in adults following prior therapy as a single agent; or

Metastatic Renal Cell Carcinoma

• As treatment of metastatic renal cell carcinoma in combination with interferon alfa; or

 Persistent, Recurrent, or Metastatic Carcinoma of the Cervix

• For the treatment of persistent, recurrent, or metastatic carcinoma of the cervix in combination with ONE of the following:
  • Paclitaxel and cisplatin; or
  • Paclitaxel and topotecan.

 The use of bevacizumab (Mvasi) for any other oncologic indication is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

The use of bevacizumab-bvzr (Zirabev®) may be considered medically necessary when ANY of the following criteria are met for the following conditions:

Metastatic Colorectal Cancer

• As first or second line treatment of individuals with metastatic colorectal cancer in combination with intravenous fluorouracil-based chemotherapy; or
• As second-line treatment of individuals with metastatic colorectal cancer who have progressed on first-line bevacizumab product-containing regimen in combination with ONE of the following:
  • Fluoropyrimidine-irinotecan; or
  • Fluoropyrimidine-oxaliplatin; or

Non-Squamous Non-Small Cell Lung Cancer

• As first line treatment in individuals with unresectable, locally advanced, recurrent or metastatic disease in combination with carboplatin and paclitaxel; or

Recurrent Glioblastoma

• For treatment of recurrent glioblastomas in individuals 18 years of age and older; or

Metastatic Renal Cell Carcinoma

• For the treatment of metastatic renal cell carcinoma in combination with interferon alfa; or

Persistent, Recurrent, or Metastatic Carcinoma of the Cervix

• For the treatment of individuals with persistent, recurrent or metastatic cervical cancer in combination with ONE of the following:
  • Paclitaxel and cisplatin; or
  • Paclitaxel and topotecan.

The use of bevacizumab (Zirabev) for any other oncologic indication is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

*Note: Bevacizumab (Avastin)-containing regimens should be used with caution and withheld for at least 6 weeks prior to interval debulking surgery due to potential interference with postoperative healing.

**Note: Pemetrexed-based chemotherapy may also be used for malignant peritoneal mesothelioma, pericardial mesothelioma, and tunica vaginalis testis mesothelioma.

Limitation of Use; Bevacizumab-awwb (Mvasi) and bevacizumab-bvzr (Zirabev) are not indicated for adjuvant treatment of colon cancer.

The effectiveness of bevacizumab products in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with bevacizumab products.

Diagnosis Codes

Covered Diagnosis Codes for Procedure Code J9035

Covered Diagnosis Codes for Procedure Code Q5107, Q5118

Links