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.
Bevacizumab-awwb (Mvasi®) and bevacizumab-bvzr (Zirabev®) are biosimilars of bevacizumab (Avastin).
Preferred Products
Bevacizumab-awwb (Mvasi) and bevacizumab-bvzr (Zirabev) are the preferred bevacizumab biosimilars for individuals initiating new therapy for oncologic indications when the clinical criteria within this policy are met. A non-preferred product will be considered when the individual has a documented therapy failure after an adequate therapeutic trial of a preferred product, or the preferred product has not been tolerated or is contraindicated.
Adequate therapeutic trial is defined as 180 days from first dose of therapy at Food and Drug Administration (FDA) or compendia based therapeutic doses of preferred product.
New therapy is defined as no previous utilization within the last 180 days calendar days.
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; or
Glioblastoma
- For treatment of recurrent glioblastoma in individuals 18 years of age and older; or
Hepatocellular Carcinoma
- For the treatment of individuals with unresectable or metastatic hepatocellular carcinoma in combination with atezolizumab who have not received prior systemic therapy; 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.
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 unresectable (local or regional) or stage IV (M1) invasive breast cancer human epidermal growth factor receptor 2 (HER2)-negative disease in ANY of the following:
- Hormone receptor-negative disease; or
- That is hormone receptor-positive with visceral crisis or 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 carmustine, lomustine, or temozolomide if bevacizumab (Avastin) monotherapy fails and it is desirable to continue the steroid sparing effects of bevacizumab (Avastin); or
- For the treatment of recurrent glioblastomas as ANY of the following:
- As a single agent; or
- In combination with carmustine, lomustine, or temozolomide if bevacizumab (Avastin) monotherapy fails and it is desirable to continue the steroid sparing effects of bevacizumab (Avastin); or
- As single-agent treatment of adult intracranial and spinal ependymoma, excluding subependymoma, for progression or current disease in individuals who are refractory to surgery or radiation therapy, if received prior radiation therapy and ANY of the following:
- Gross total or subtotal resection with negative cerebrospinal fluid (CSF) cytology; or
- Subtotal resection and evidence of metastasis (brain, spine, or CSF); or
- Unresectable disease; 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
- Metastatic spine tumors; or
Cervical Cancer
- As first-line therapy, or second-line therapy as clinically appropriate if not used previously as first-line, in combination with paclitaxel and cisplatin or carboplatin, or in combination with paclitaxel and topotecan, or second-line therapy as a single agent for EITHER of the following:
- Local/regional recurrence; or
- Stage IVB or distant metastases; or
- Second-line therapy for persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC)
- In combination with paclitaxel and cisplatin; or
- In combination with paclitaxel and carboplatin; or
- In combination with paclitaxel and topotecan; or
- As a single agent; or
Colon Cancer
- As therapy in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin and irinotecan), CapeOX (capecitabine and oxaliplatin), or FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in individuals appropriate for intensive therapy in ANY of the following:
- As primary treatment for locally unresectable or medically inoperable disease; or
- For unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy; or
- As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction; or
- For synchronous unresectable metastases of other sites; or
- As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy; or
- For unresectable metachronous metastases that remain unresectable after primary treatment and progressed on non-intensive therapy, except if received previous fluoropyrimidine, with improvement in functional status; or
- As adjuvant treatment following synchronized or staged resection for synchronous liver and/or lung metastases that converted from unresectable to resectable disease after primary treatment; or
- As adjuvant treatment (following resection and/or local therapy) for resectable metachronous metastases in individuals who have received previous chemotherapy; or
- As adjuvant treatment for unresectable metachronous metastases that converted to resectable disease after primary treatment; or
- As therapy in combination with capecitabine or 5-FU/LV regimen in individuals who are NOT appropriate for intensive therapy in ANY of the following:
- As primary treatment for locally unresectable or medically inoperable disease; or
- For unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy; or
- As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction; or
- For synchronous unresectable metastases of other sites; or
- As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy; or
- For unresectable metachronous metastases that remain unresectable after primary treatment; or
- As adjuvant therapy following synchronized or staged resection for synchronous liver and/or lung metastases that converted from unresectable to resectable disease after primary treatment; or
- As adjuvant treatment (following resection and/or local therapy) for resectable metachronous metastases in individuals who have received previous chemotherapy; or
- As adjuvant treatment for unresectable metachronous metastases that converted to resectable disease 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
- 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 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; or
- As adjuvant in combination with irinotecan for unresectable metachronous metastases that converted to resectable disease after primary treatment; or
- Subsequent therapy for progression of advanced or metastatic disease in combination with trifluridine and tipiracil in individuals who have progressed through all available regimens and previously received;
- Oxaliplatin-based therapy without irinotecan; or
- Irinotecan-based therapy without oxaliplatin; or
- Treatment with oxaliplatin and irinotecan; or
- Therapy without irinotecan or oxaliplatin; or
- Without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab; or
Hepatobiliary Cancer
- As first-line treatment in combination with atezolizumab for individuals Child-Pugh Class A only who have ANY of the following:
- Unresectable disease and are not a transplant candidate; or
- Are inoperable by performance status or comorbidity, or have local disease or local disease with minimal extrahepatic disease only; or
- Metastatic disease or extensive liver tumor burden; or
Kidney Cancer
- As therapy for relapse or stage IV disease in ANY of the following:
- 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, or in individuals not eligible for cisplatin in combination with pemetrexed and 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 or biphasic histology; or
- Treatment of clinical stage IIIB or IV disease, sarcomatoid, or medically inoperable tumors in individuals with performance status (PS) 0-2; or
Non-Small Cell Lung Cancer
- Therapy in combination with erlotinib for sensitizing EGFR mutation-positive nonsquamous cell histology, recurrent, advanced or metastatic disease with no history of hemoptysis as EITHER of the following:
- First-line therapy; or
- Continuation of therapy following disease progression on combination or erlotinib with bevacizumab for asymptomatic disease, symptomatic brain lesions, or isolated symptomatic systemic lesions; or
- Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (greater than or equal to 1%) tumors that are EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation, and RET negative and no contraindications to PD-1 or PD-L1 inhibitors 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 PD-1 or PD-L1 inhibitors) or in combination with cisplatin and pemetrexed, or in combination with atezolizumab, carboplatin, and paclitaxel 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, MET exon 14 skipping mutation, RET negative, and PD-L1 less than 1%; or
- First line or subsequent therapy for BRAF V600E-mutation positive tumors; or
- First line or subsequent therapy for NTRK gene fusion positive tumors; or
- First line or subsequent therapy for MET exon 14 skipping mutation positive tumors; or
- First line or subsequent therapy for RET rearrangement 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 1%) tumors and EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation, and RET negative and no prior platinum-doublet chemotherapy but with a PD-1/PD-L1 inhibitor; or
- Continuation maintenance therapy in combination with atezolizumab for recurrent, advanced, or metastatic disease for PD-L1 expression positive (greater than or equal to 1%) tumors that are EGFR, ALK, ROS1, BRAF, MET exon 14 skipping mutation, and RED negative and no contraindications to PD-1 or PD-L1 inhibitors in individuals with performance status 0-2 who achieve tumor response or stable disease following first-line therapy with atezolizumab/carboplatin/paclitaxel/bevacizumab (Avastin) for nonsquamous cell histology; or
- Continuation maintenance therapy for recurrent, advanced, or metastatic disease with PD-L1 expression <1% 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 initial systemic therapy:
- 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 regimen and no contraindications to PD-1 or PD-L1 inhibitors; or
Ovarian Epithelial Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer
- As single agent therapy for persistent disease or recurrence in ANY of the following:
- As immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy; or
- For progression on primary, maintenance, or recurrence therapy; or
- For stable or persistent disease if not on maintenance therapy; or
- For complete remission and relapse less than 6 months after completing chemotherapy; or
- For radiographic and/or clinical relapse in individuals with previously complete remission and relapse after 6 months or greater after completing prior chemotherapy; or
- Used in combination with paclitaxel and carboplatin for individuals who are poor surgical candidates or have a low likelihood of optimal cytoreduction as ANY of the following:
- Neoadjuvant therapy; or
- Continued treatment for stable disease following neoadjuvant therapy; or
- Adjuvant therapy following interval debulking surgery (IDS) in individuals with response or stable disease to neoadjuvant therapy; or
- Used in combination with paclitaxel and carboplatin as primary adjuvant therapy for pathologic stage II-IV disease; or
- As maintenance therapy as a single agent for stage II-IV disease if complete clinical remission or partial remission to primary therapy including bevacizumab (Avastin) in EITHER of the following:
- As a single agent or in combination with olaparib in individuals BRCA 1/2 wild-type or unknown; or
- In combination with olaparib in individuals with a germline or somatic BRCA 1/2 mutation; 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
- Used in combination with ANY of the following if platinum-sensitive persistent disease or recurrence:
- Carboplatin and gemcitabine; or
- Carboplatin and paclitaxel; or
- Carboplatin and liposomal doxorubicin; or
- Fluorouracil, leucovorin, and oxaliplatin for mucinous carcinoma; or
- Capecitabine and oxaliplatin for mucinous carcinoma; or
- As immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy; or
- In individuals with complete remission and relapse 6 months or greater after completing prior chemotherapy; or
- As adjuvant treatment in combination with carboplatin and paclitaxel for pathologic stage II-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 adjuvant treatment in combination with carboplatin and paclitaxel for pathologic stage II-IV low-grade serous 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
- As adjuvant treatment in combination with carboplatin and paclitaxel for pathologic stage II-IV, grade 1 endometrioid carcinoma; or
- As targeted therapy in combination with niraparib in platinum-sensitive persistent disease or recurrence in ANY of the following:
- As immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy; or
- For radiographic and/or clinical relapse in individuals with previous complete remission and relapse after 6 months or greater after completing prior chemotherapy; or
- As therapy for platinum-resistant persistent disease or recurrent in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan in ANY of the following:
- As immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy; or
- For progression on primary, maintenance, or recurrence therapy; or
- Stable or persistent disease, if not on maintenance therapy; or
- For complete remission and relapse less than 6 months after completing chemotherapy; or
- As maintenance therapy as a single agent if used previously as part of a combination therapy for individuals with partial or complete response following recurrence therapy with chemotherapy plus bevacizumab (Avastin) for platinum-sensitive 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
- As therapy in combination with capecitabine or 5-FU/LV regimen in individuals NOT appropriate for intensive therapy in ANY of the following:
- Adjuvant treatment following resection and/or local therapy for resectable metachronous metastases in individuals who received previous chemotherapy; or
- Adjuvant treatment for unresectable metachronous metastases that converted to resectable disease after primary treatment; 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 palliative radiation therapy (RT) or chemotherapy/RT 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 nonobstructing, or following local therapy for individuals with existing or imminent obstruction; or
- As primary treatment for synchronous unresectable metastases of other sites; or
- As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous 5-FU/LV or capecitabine therapy, or who have not received any previous chemotherapy; or
- For unresectable metachronous metastases that remain unresectable after primary treatment; or
- Used in combination with FOLFOX, FOLFIRI, CapeOX, or FOLFOXIRI regimen in individuals appropriate for intensive therapy in ANY of the following:
- Adjuvant treatment following resection and/or local therapy for resectable metachronous metastases in individuals who have received previous chemotherapy; or
- Adjuvant treatment for unresectable metachronous metastases that converted to resectable disease after primary treatment; 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 palliative radiation therapy (RT) or chemotherapy/RT 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 nonobstructing, or following local therapy for individuals with existing or imminent obstruction; or
- As primary treatment for synchronous unresectable metastases of other sites; or
- As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous 5-FU/LV or capecitabine therapy, or who have not received any previous chemotherapy; or
- For unresectable metachronous metastases that remain unresectable after primary treatment and progressed on non-intensive therapy, except if received previously fluoropyrimidine with improvement in functional status; or
- As adjuvant treatment in combination with irinotecan for unresectable metachronous metastases that converted to resectable disease after primary treatment; 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
- 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
Small Bowel Adenocarcinoma
- As initial therapy in combination with FOLFOX, CapeOX, or FOLFOXIRI regimen for advanced or metastatic disease in individuals appropriate for intensive therapy; or
- As initial therapy in combination with capecitabine or 5-FU/LV regimen for advanced or metastatic disease in individuals NOT appropriate for intensive therapy; or
Soft Tissue Sarcoma: Angiosarcoma
- As single agent therapy for angiosarcoma; or
Soft Tissue Sarcoma: Solitary Fibrous Tumor
- In combination with temozolomide for the treatment of solitary fibrous tumor; 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 inguinofemoral/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.
The use of bevacizumab-awwb (Mvasi) may be considered medically necessary when ANY of the following criteria are met for the following conditions:
Food and Drug Administration (FDA) Indications
Glioblastoma
- As treatment for recurrent glioblastoma in individuals 18 years of age and older; or
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
Metastatic Renal Cell Carcinoma
- As treatment of metastatic renal cell carcinoma in combination with interferon alfa; 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
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.
The use of bevacizumab-bvzr (Zirabev) may be considered medically necessary when ANY of the following criteria are met for the following conditions:
Food and Drug Administration (FDA) Indications
Glioblastoma
- For treatment of recurrent glioblastoma in individuals 18 years of age and older; or
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
Metastatic Renal Cell Carcinoma
- For the treatment of metastatic renal cell carcinoma in combination with interferon alfa; 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
Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
· Treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with ANY of the following:
o Carboplatin and paclitaxel, followed by bevacizumab (Zirabev) as a single agent, for stage III or IV disease following initial surgical resection; or
o Paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than two (2) prior chemotherapy regimens; or
o Carboplatin and paclitaxel or carboplatin and gemcitabine, followed by bevacizumab (Zirabev) as a single agent, for platinum-sensitive recurrent disease; 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.
The use of bevacizumab-awwb (Mvasi) or bevacizumab-bvzr (Zirabev) may be considered medically necessary as a substitute for bevacizumab (Avastin) for ANY of the following conditions:
National Comprehensive Cancer Network (NCCN) Recommendations
- Central Nervous system cancers:
- Cervical Cancer; or
- Colon Cancer; or
- Hepatocellular Carcinoma; or
- Kidney Cancer; or
- Malignant Pleural Mesothelioma; or
- Non-Small Cell Lung Cancer; or
- Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancers:
- Carcinosarcoma (Malignant Mixed Mullerian Tumors); or
- Clear Cell Carcinoma; or
- Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer; or
- Grade 1 Endometrioid Carcinoma; or
- Low-Grade Serous Carcinoma/Ovarian Borderline Epithelial Tumors (Low Malignant Potential) with Invasive Implants; or
- Malignant Sex Cord-Stromal Tumors; or
- Mucinous Carcinoma; or
- Rectal Cancer; or
- Squamous Cell Carcinoma- Vulvar Cancer; or
- Small bowel adenocarcinoma: or
- Small bowel advanced ampullary cancer; or
- Uterine Neoplasms- Endometrial Carcinoma.
The use of bevacizumab (Mvasi, 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.
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. Highmark 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.
Note: Biologic therapy is only appropriate for continuation of favorable response from conversion therapy.
If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes.
Refer to Medical Policy Bulletin I-94 for eligibility guidelines for the use of Avastin for intravitreal injections.
Covered Diagnosis Codes for Procedure Code J9035
C17.0
|
C17.1
|
C17.2
|
C17.3
|
C17.8
|
C17.9
|
C18.0
|
C18.1
|
C18.2
|
C18.3
|
C18.4
|
C18.5
|
C18.6
|
C18.7
|
C18.8
|
C18.9
|
C19
|
C20
|
C21.8
|
C22.0
|
C22.3
|
C22.8
|
C22.9
|
C33
|
C34.00
|
C34.01
|
C34.02
|
C34.10
|
C34.11
|
C34.12
|
C34.2
|
C34.30
|
C34.31
|
C34.32
|
C34.80
|
C34.81
|
C34.82
|
C34.90
|
C34.91
|
C34.92
|
C38.4
|
C45.0
|
C45.1
|
C46.0
|
C46.1
|
C46.2
|
C46.3
|
C46.4
|
C46.50
|
C46.51
|
C46.52
|
C46.7
|
C46.9
|
C48.0
|
C48.1
|
C48.2
|
C48.8
|
C49.0
|
C49.10
|
C49.11
|
C49.12
|
C49.20
|
C49.21
|
C49.22
|
C49.3
|
C49.4
|
C49.5
|
C49.6
|
C49.8
|
C49.9
|
C50.011
|
C50.012
|
C50.019
|
C50.021
|
C50.022
|
C50.029
|
C50.111
|
C50.112
|
C50.119
|
C50.121
|
C50.122
|
C50.129
|
C50.211
|
C50.212
|
C50.219
|
C50.221
|
C50.222
|
C50.229
|
C50.311
|
C50.312
|
C50.319
|
C50.321
|
C50.322
|
C50.329
|
C50.411
|
C50.412
|
C50.419
|
C50.421
|
C50.422
|
C50.429
|
C50.511
|
C50.512
|
C50.519
|
C50.521
|
C50.522
|
C50.529
|
C50.611
|
C50.612
|
C50.619
|
C50.621
|
C50.622
|
C50.629
|
C50.811
|
C50.812
|
C50.819
|
C50.821
|
C50.822
|
C50.829
|
C50.911
|
C50.912
|
C50.919
|
C50.921
|
C50.922
|
C50.929
|
C51.0
|
C51.1
|
C51.2
|
C51.8
|
C51.9
|
C53.0
|
C53.1
|
C53.8
|
C53.9
|
C54.0
|
C54.1
|
C54.2
|
C54.3
|
C54.8
|
C54.9
|
C55
|
C56.1
|
C56.2
|
C56.9
|
C57.00
|
C57.01
|
C57.02
|
C57.10
|
C57.11
|
C57.12
|
C57.20
|
C57.21
|
C57.22
|
C57.3
|
C57.4
|
C57.7
|
C57.8
|
C57.9
|
C64.1
|
C64.2
|
C64.9
|
C65.1
|
C65.2
|
C65.9
|
C70.0
|
C70.1
|
C70.9
|
C71.0
|
C71.1
|
C71.2
|
C71.3
|
C71.4
|
C71.5
|
C71.6
|
C71.7
|
C71.8
|
C71.9
|
C72.0
|
C72.9
|
C78.00
|
C78.01
|
C78.02
|
C78.6
|
C78.7
|
C79.31
|
C79.32
|
C79.82
|
C79.89
|
C79.9
|
C83.30
|
C83.31
|
C83.39
|
C83.80
|
C83.81
|
C83.89
|
C85.89
|
D32.0
|
D32.1
|
D32.9
|
D42.0
|
D42.1
|
D42.9
|
D43.0
|
D43.1
|
D43.2
|
D43.4
|
I67.89
|
Z85.038
|
Z85.068
|
Z85.118
|
Z85.3
|
Z85.43
|
Z85.528
|
Z85.831
|
Z85.841
|
Z85.848
|
|
|
Covered Diagnosis Codes for Procedure Code Q5107, Q5118
C17.0
|
C17.1
|
C17.2
|
C17.8
|
C17.9
|
C18.0
|
C18.1
|
C18.2
|
C18.3
|
C18.4
|
C18.5
|
C18.6
|
C18.7
|
C18.8
|
C18.9
|
C19
|
C20
|
C21.8
|
C22.0
|
C22.8
|
C22.9
|
C33
|
C34.00
|
C34.01
|
C34.02
|
C34.10
|
C34.11
|
C34.12
|
C34.2
|
C34.30
|
C34.31
|
C34.32
|
C34.80
|
C34.81
|
C34.82
|
C34.90
|
C34.91
|
C34.92
|
C38.4
|
C45.0
|
C45.1
|
C48.1
|
C48.2
|
C48.8
|
C51.0
|
C51.1
|
C51.2
|
C51.8
|
C51.9
|
C53.0
|
C53.1
|
C53.8
|
C53.9
|
C54.0
|
C54.1
|
C54.2
|
C54.3
|
C54.8
|
C54.9
|
C55
|
C56.1
|
C56.2
|
C56.9
|
C57.00
|
C57.01
|
C57.02
|
C57.10
|
C57.11
|
C57.12
|
C57.20
|
C57.21
|
C57.22
|
C57.3
|
C57.4
|
C57.7
|
C57.8
|
C57.9
|
C64.1
|
C64.2
|
C64.9
|
C65.1
|
C65.2
|
C65.9
|
C71.0
|
C71.1
|
C71.2
|
C71.3
|
C71.4
|
C71.5
|
C71.6
|
C71.7
|
C71.8
|
C71.9
|
C72.0
|
C72.9
|
C78.00
|
C78.01
|
C78.02
|
C78.6
|
C78.7
|
C79.82
|
Z85.118
|
Z85.038
|
Z85.068
|
Z85.43
|
Z85.841
|
|
|
|
|
|
|
Place of Service: Outpatient
Experimental/Investigational (E/I) services are not covered regardless of place of service.
The administration of bevacizumab (Avastin) is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.
The policy position applies to all commercial lines of business
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical or other circumstances may warrant individual consideration, based on review of applicable medical records, as well as other regulatory, contractual and/or legal requirements.
Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract, and subject to the applicable laws of your state.
Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.
Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
- Provides free aids and services to people with disabilities to communicate effectively with us, such as:
- Qualified sign language interpreters
- Written information in other formats (large print, audio, accessible electronic formats, other formats)
- Provides free language services to people whose primary language is not English, such as:
- Qualified interpreters
- Information written in other languages
If you need these services, contact the Civil Rights Coordinator.
If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.
You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:
U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)
Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.
Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.
Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.
Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
Provides free aids and services to people with disabilities to communicate effectively with us, such as:
Qualified sign language interpreters Written information in other formats (large print, audio, accessible electronic formats, other formats)
Provides free language services to people whose primary language is not English, such as:
Qualified interpreters Information written in other languages
If you need these services, contact the Civil Rights Coordinator.
If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295
, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.
You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:
U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)
Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.
