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Bevacizumab (Avastin®) and Related Biosimilars For Oncologic Use
MA08.072j

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.
This policy addresses numerous medically necessary indications* for the use of bevacizumab (Avastin®), bevacizumab-awwb (Mvasi™), bevacizumab-bvzr (Zirabev™) in the following cancers (listed in order of appearance within the Policy section)

​Central nervous system tumors
​​Malignant pleural mesothelioma
​Cervical carcinoma
​​​Non-squamous non-small cell lung cancer
​Colon carcinoma
​Ovarian (epithelial), fallopian tube, primary peritoneal cancers
​Rectal carcinoma
​Soft tissue sarcoma
​Small bowel adenocarcinoma/ advanced ampullary cancer
Uterine/ endometrial cancers
​Hepatocellular carcinoma
Vulvar cancer
​Kidney cancer
*Indications for single-agent therapy, preferred second-line therapy, subsequent therapy, relapsed or refractory therapy, pediatric and adult treatment, and limitations of use are all addressed within each section of specific cancer.​ ​

MEDICALLY NECESSARY

COMPANY-DESIGNATED PREFERRED PRODUCTS
Although there are many bevacizumab products on the market (e.g., bevacizumab [Avastin®], bevacizumab-awwb [Mvasi™], bevacizumab-bvzr [Zirabev™]), there is no reliable evidence of the superiority of any one product of bevacizumab compared to other products. The Company has designated the following bevacizumab biosimilar products as its preferred products: bevacizumab-awwb (Mvasi™) and bevacizumab-bvzr (Zirabev™).

These products are less costly and at least as likely to produce equivalent therapeutic results as the non-preferred products, which includes, but are not limited to bevacizumab (Avastin®) and any other non-preferred bevacizumab biosimilars.

According to the United States Food and Drug Administration (FDA) “a biosimilar is a biological product that has no clinically meaningful differences from the existing FDA-approved reference product. All biosimilar products meet the FDA’s rigorous standards for approval for the indications described in the product labeling. Once a biosimilar has been approved by the FDA, the safety and effectiveness of these products have been established, just as they have been for the reference product.”

NON-PREFERRED PRODUCTS
Use of non-preferred products, bevacizumab (Avastin®) or any non-preferred biosimilar,​​​ is considered medically necessary and, therefore, covered only for individuals who are currently receiving or have previously received a non-preferred product for the specified bevacizumab indication.

If the individual has not previously received non-preferred product to treat the specified indication, these non-preferred products are eligible for coverage when the individual has documented contraindication(s) or intolerance(s) to the Company designated preferred products.

BEVACIZUMAB AND RELATED BIOSIMILARS
Bevacizumab and related biosimilars are considered medically necessary and, therefore, covered for the following indications when the dosing and frequency requirements listed in Attachment A and the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NON-PREFERRED PRODUCTS Sections above are met:

CENTRAL NERVOUS SYSTEM TUMORS
  • Treatment of recurrent anaplastic glioma or ​recurrent glioblastoma​ disease as a single agent (National Comprehensive Cancer Network​ [NCCN]-preferred) or in combination with carmustine, lomustine, or temozolomide if bevacizumab monotherapy fails and it is desirable to continue the steroid sparing effects of bevacizumab 
  • As short-course single agent therapy for management of symptoms driven by radiation therapy (RT) necrosis, poorly controlled vasogenic edema, or mass effect for any of the following conditions:
    • Adult low-grade (WHO grade I or II) glioma 
    • Anaplastic glioma
    • Glioblastoma
    • Adult intracranial and spinal ependymoma (excludes subependymoma)
    • Adult medulloblastoma
    • Primary central nervous system lymphoma
    • Meningiomas
    • Brain metastases (limited or extensive)
    • Metastatic spine tumors
    • Limited Brain Metastases
  • Treatment as a single-agent for disease progression or recurrent adult intracranial and spinal ependymoma (excludes subependymoma) in individuals who are refractory to surgery or RT, if received prior RT and individuals has any of the following:
    • ​gross total or subtotal resection with negative cerebrospinal fluid (CSF) cytology
    • subtotal resection​ and evidence of metastasis (brain, spine, or CSF)
    • ​unresectable disease
  • ​​Treatment as a single agent for surgically inaccessible recurrent or progressive meningiomas when radiation is not possible.
CERVICAL CARCINOMA
  • In combination with paclitaxel and cisplatin or paclitaxel and topotecan for persistent, recurrent, or metastatic carcinoma of the cervix 
  • First-line, second or subsequent  line therapy as clinically appropriate (if not used previously as first-line) for local/regional recurrence or Stage IVB or distant metastases in combination with paclitaxel and cisplatin (NCCN-preferred regimen), paclitaxel and carboplatin (NCCN-preferred regimen), or paclitaxel and topotecan 
  • First-line, second or subsequent  line therapy as clinically appropriate (if not used previously as first-line) in combination with pembrolizumab, paclitaxel, and cisplatin or carboplatin (NCCN-preferred regimen)​ for PD-L1 positive (combined positive score [CPS] ≥1) as determined by an FDA-approved test 
  • Second-line therapy for persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC) 
    • ​in combination with pembrolizumab, cisplatin, and paclitaxel if PD-L1 positive (combined positive score [CPS] ≥1) as determined by an FDA-approved test (preferred) 
    • in combination with pembrolizumab, carboplatin, and paclitaxel if PD-L1 positive (CPS ≥1) as determined by an FDA-approved test (preferred) 
    • ​​in combination with paclitaxel and cisplatin (NCCN-preferred regimen)
    • in combination with paclitaxel and carboplatin (NCCN-preferred regimen)​
    • in combination with paclitaxel and topotecan ​

COLON OR RECTAL CARCINOMA: 
Colorectal carcinoma

  • In individuals who have metastatic carcinoma of the colon or rectum, as a second-line treatment in individuals who have progressed on a first-line bevacizumab (or related biosimilar) regimen, in combination with fluoropyrimidine-, irinotecan-, or fluoropyrimidine-oxaliplatin--based chemotherapy
Colon carcinoma

  • For colon carcinoma, as ​primary treatment for unresectable synchronous liver and/or lung metastases in combination with one of the following regimens:
    • FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen
    • FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
    • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen
    • CapeOX (capecitabine and oxaliplatin) regimen
  • As subsequent therapy for progression of advanced or metastatic disease for any of the following indications
    • as the preferred anti-angiogenic agent in combination with irinotecan or FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen if previously treated with oxaliplatin-based therapy without irinotecan
    • in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) regimen if previously treated with irinotecan-based therapy without oxaliplatin
    • as the preferred anti-angiogenic agent in combination with irinotecan or FOLFIRI if previously treated without irinotecan or oxaliplatin
    • in combination with FOLFOX, CapeOX, or irinotecan and oxaliplatin if previously treated without irinotecan or oxaliplatin 

  • ​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 for any of the following indications: 
    • as primary treatment for locally unresectable or medically inoperable disease
    • for unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy
    • as primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals​ with existing or imminent obstruction
    • for synchronous unresectable metastases of other sites
    • 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
    • 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
  • As 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 for any of the following indications: 
    • oxaliplatin-based therapy without irinotecan
    • irinotecan-based therapy without oxaliplatin
    • treatment with oxaliplatin and irinotecan
    • therapy without irinotecan or oxaliplatin
    • without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab
  • In combination with capecitabine or with 5-FU/leucovorin (fluorouracil and leucovorin) regimen, in individuals not appropriate for intensive therapy  for any of the following indications:​
    • as primary treatment for locally unresectable or medically inoperable disease
    • for unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy
    • as primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction
    • for synchronous unresectable metastases of other sites
    • 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
    • for unresectable metachronous metastases that remain unresectable after primary treatment
  • As NCCN preferred anti-angiogenic therapy as primary treatment for individuals with unresectable metachronous metastases and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months  for any of the following indications: 
    • in combination with irinotecan
    • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen 
Rectal carcinoma

  • In combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan) or CapeOX (capecitabine and oxaliplatin) regimen​ as primary treatment for T3, N Any; T1-2, N1-2; T4, N Any; or locally unresectable or medically inoperable disease if resection is contraindicated following neoadjuvant therapy, in individuals appropriate for intensive therapy
  • In combination with capecitabine or 5-FU/leucovorin (fluorouracil and leucovorin) regimen​ as primary treatment for T3, N Any; T1-2, N1-2; T4, N Any; or locally unresectable or medically inoperable disease if resection is contraindicated following neoadjuvant therapy, in individuals not appropriate for intensive therapy ​
  • In combination with FOLFOX, FOLFIRI, CapeOX, ​or FOLFOXIRI regimen, in individuals appropriate for intensive therapy 
    • 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
    • ​following palliative short-course radiation therapy (RT) or chemo/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
    • as primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction
    • as primary treatment for synchronous unresectable metastases of other sites
    • as primary treatment for unresectable isolated pelvic/anastomotic recurrence​
    • 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
    • for unresectable metachronous metastases that remain unresectable after primary treatment
    • for progression on non-intensive therapy, except if received previous fluoropyrimidine, with improvement in functional status ​​
  • In combination with capecitabine or 5-FU/leucovorin (fluorouracil and leucovorin) regimen in individuals not appropriate for intensive therapy

    • 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
    • following palliative radiation therapy (RT) or chemo/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
    • as primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction
    • as primary treatment for synchronous unresectable metastases of other sites
    • ​as primary treatment for unresectable isolated pelvic/anastomotic recurrence​
    • 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
    • for unresectable metachronous metastases that remain unresectable after primary treatment​
  • ​​​​​​​​Primary treatment for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable in combination with one of the following:
  • FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
  • FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen
  • CapeOX (capecitabine and oxaliplatin) regimen
  • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen​  
  • Primary treatment as NCCN preferred anti-angiogenic therapy for individuals with unresectable metachronous metastases and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
  • in combination with irinotecan
  • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen 
  • Subsequent therapy for progression of advanced or metastatic disease
    • as the preferred anti-angiogenic agent in combination with irinotecan or FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen if previously treated with oxaliplatin-based therapy without irinotecan
    • in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) regimen if previously treated with irinotecan-based therapy without oxaliplatin
    • as the preferred anti-angiogenic agent in combination with irinotecan or FOLFIRI if previously treated without irinotecan or oxaliplatin
    • in combination with FOLFOX, CapeOX, or irinotecan and oxaliplatin if previously treated without irinotecan or oxaliplatin
  • 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
    • irinotecan-based therapy without oxaliplatin
    • treatment with oxaliplatin and irinotecan
    • therapy without irinotecan or oxaliplatin
    • without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab

SMALL BOWEL ADENOCARCINOMA // ADVANCED AMPULLARY CANCER

 

  • In combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), CapeOX (capecitabine and oxaliplatin), or FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen for advanced or metastatic disease in  individuals appropriate for intensive therapy
    • as initial therapy
    • as subsequent therapy in individuals who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab
  • In combination with capecitabine or 5-FU/leucovorin (fluorouracil and leucovorin) regimen for advanced or metastatic disease in individuals not appropriate for intensive therapy
    • as initial therapy
    • as subsequent therapy in individuals who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab
  • In combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), CapeOX (capecitabine and oxaliplatin), or FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen for advanced or metastatic disease in individuals appropriate for intensive therapy
    • as initial therapy
    • ​as subsequent therapy in individuals who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab

  • In combination with capecitabine or 5-FU/leucovorin (fluorouracil and leucovorin) regimen for advanced or metastatic disease in individuals not appropriate for intensive therapy
    • as initial therapy
    • as subsequent therapy in individuals who previously received initial therapy with nivolumab with or without ipilimumab, or pembrolizumab 
HEPATOCELLULAR CARCINOMA 
  • ​In individuals with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy, in combination with atezolizumab (Tecentriq)  

  • ​As NCCN preferred first-line treatment in combination with atezolizumab for individuals (Child-Pugh Class A only) for individuals​ who have any of the following indications:
    • unresectable disease and are not a transplant candidate
    • liver-confined disease, inoperable by performance status, comorbidity or with minimal or uncertain extrahepatic disease
    • metastatic disease or extensive liver tumor burden 
KIDNEY CARCINOMA
  • In individuals who have metastatic renal cell carcinoma (mRCC) in combination with interferon alpha 
  • In individuals with relapsed or stage IV kidney cancer with one of the following conditions:
    • non-clear cell histology as a single agent
    • in combination with erlotinib for non-clear cell histology in selected individuals with advanced papillary renal cell carcinoma including hereditary leiomyomatosis and renal cell carcinoma (HLRCC) associated RCC
    • in combination with everolimus as systemic therapy for non-clear cell histology

MALIGNANT PLEURAL MESOTHELIOMA 
 In combination with pemetrexed and either cisplatin (NCCN-preferred regimen) or carboplatin (in individuals not eligible for cisplatin) followed by single-agent maintenance bevacizumab as treatment of one of the following:
  • unresectable clinical stage I-IIIA disease and tumors of epithelial histology or sarcomatoid or mixed biphasic histology
  • clinical stage IIIB or IV disease, sarcomatoid, or medically inoperable tumors in individuals with performance status (PS) 0-2

NON-SQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC): ADENOCARCINOMA  AND LARGE CELL CARCINOMA
  • In individuals who have unresectable, locally advanced, recurrent, or metastatic NSCLC, as first-line treatment in combination with paclitaxel (Taxol®) and carboplatin (Paraplatin®)
  • In combination with erlotinib for EGFR mutation-positive (eg, exon 19 deletion or L858R) nonsquamous cell histology, recurrent, advanced, or metastatic disease with no history of hemoptysis as (Except for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease) either first-line therapy or continuation of therapy following disease progression on combination of erlotinib with bevacizumab for asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited metastases

  • Treatment for recurrent, advanced, or metastatic disease** as first-line therapy for PD-L1 expression positive (≥1%) tumors that are EGFR, ALK, ROS1, BRAF, MET 14 skipping mutation, and RET negative or unknown and no contraindications to PD-1 or PD-L1 inhibitors the addition of pembrolizumab or atezolizumab and performance status (PS) 0-2 in combination with atezolizumab, carboplatin and paclitaxel for nonsquamous cell histology 
  • Treatment 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 combination with:
  • (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease) 

    • carboplatin and either paclitaxel or pemetrexed (useful in certain circumstances, if contraindications** to PD-1 or PD-L1 inhibitors)
    • cisplatin and pemetrexed (useful in certain circumstances, if contraindications** to PD-1 or PD-L1 inhibitors)

    The above regimens are used as:

    • initial systemic therapy for PD-L1 expression positive (≥1%) and negative for actionable molecular markers* with contraindications to PD-1 or PD-L1 inhibitors
    • initial systemic therapy for PD-L1 <1% and negative for actionable molecular markers*
    • first-line therapy for EGFR exon 20 mutation positive tumors
    • first-line therapy for KRAS G12C mutation positive tumors
    • first-line (useful in certain circumstances) or subsequent therapy for BRAF V600E mutation positive tumors
    • first-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion positive tumors
    • first-line (useful in certain circumstances) or subsequent therapy for MET exon 14 skipping mutation positive tumors
    • first-line or subsequent therapy for RET rearrangement positive tumors
    • subsequent therapy for EGFR mutation positive (eg, exon 19 deletion or L858R) tumors and prior erlotinib +/- (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, or dacomitinib therapy
    • subsequent therapy for ALK rearrangement positive tumors and prior crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib therapy
    • subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, or ceritinib therapy
    • subsequent therapy for PD-L1 expression positive (≥1%) tumors and negative for actionable molecular markers* after prior PD-1/PD-L1 inhibitor but no prior platinum-containing chemotherapy 
  • Treatment 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 combination with atezolizumab, carboplatin and paclitaxel (if no contraindications** to PD-1 or PD-L1 inhibitors) for any of the following indications: 

    • initial systemic therapy for PD-L1 <1% and negative for actionable molecular markers*
    • first-line therapy for EGFR exon 20 mutation-positive tumors
    • first-line therapy for KRAS G12C mutation-positive tumors
    • first-line (useful in certain circumstances) or subsequent therapy for BRAF V600E mutation-positive tumors
    • first-line (useful in certain circumstances) or subsequent therapy for NTRK1/2/3 gene fusion-positive tumors
    • first-line (useful in certain circumstances) or subsequent therapy for MET exon 14 skipping mutation-positive tumors
    • subsequent therapy for ROS1 rearrangement positive tumors and prior crizotinib, entrectinib, or ceritinib therapy 
  • ​Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (≥1%) tumors that are negative for actionable molecular markers* 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 
  • Continuation maintenance therapy in combination with atezolizumab for recurrent, advanced, or metastatic disease for PD-L1 expression positive (≥1%) tumors that are negative for actionable molecular markers* and no contraindications** to PD-1 or PD-L1 inhibitors in individuals with performance status 0-2 who achieve a response or stable disease following first-line therapy with atezolizumab/carboplatin/paclitaxel/bevacizumab for nonsquamous cell histology (except for locoregional recurrence or symptomatic local disease [with the exception of mediastinal lymph node recurrence with prior radiation therapy] with no evidence of disseminated disease)
  • Continuation maintenance therapy for recurrent, advanced, or metastatic disease (except for locoregional recurrence or symptomatic local disease [with the exception of mediastinal lymph node recurrence with prior radiation therapy] with no evidence of disseminated disease) with PD-L1 expression <1% in individuals with performance status 0 to 2tumors of nonsquamous cell histology, and no history of recent hemoptysis who achieve tumor response or stable disease following initial systemic therapy, with one of the following regimens: 
    • ​as single-agent
    • in combination with pemetrexed (if previously used with a first-line pemetrexed/platinum chemotherapy regimen)
    • in combination with atezolizumab (if previously used first-line as part of an atezolizumab/carboplatin/paclitaxel/bevacizumab regimen) ​for nonsquamous cell histology and no contraindications** to PD-1 or PD-L1 inhibitors

*If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, 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
**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (eg, EGFR [exon 19 deletions, p.L858R point mutation in exon 21], ALK rearrangements, RET rearrangements), which would predict lack of benefit


OVARIAN CANCER (EPITHELIAL), FALLOPIAN TUBE CANCER, OR PRIMARY PERITONEAL CANCER

Low-Grade Serous Carcinoma/Ovarian Borderline Epithelial Tumors (Low Malignant Potential) with invasive implants, Grade 1 Endometrioid Carcinoma, Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer, Clear Cell Carcinoma

 

  • Maintenance therapy as a single agent if used previously as part of combination therapy for individuals with partial or complete response following recurrence therapy with chemotherapy plus bevacizumab for platinum-sensitive disease  

Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer/ Carcinosarcoma (Malignant Mixed Müllerian Tumors)


  • Maintenance therapy in combination with olaparib for stage II-IV carcinosarcoma with a germline or somatic BRCA1/2 mutation if complete response (CR) or partial response (PR) to primary therapy including bevacizumab  
  • Maintenance therapy as a single agent if used previously as part of combination therapy for individuals with partial or complete response following recurrence therapy with chemotherapy plus bevacizumab for platinum-sensitive disease 
  • As an NCCN-preferred​ therapy​ for rising CA-125 levels or clinical relapse in individuals who have received no prior chemotherapy in combination with paclitaxel and carboplatin 
  • Targeted therapy in combination with niraparib in platinum-sensitive persistent disease or recurrence except for immediate treatment of biochemical relapse: 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after
  • As an NCCN-preferred​​ targeted therapy as a single agent for persistent disease or recurrence except for immediate treatment of biochemical relapse 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy​​
    • for progression on primary, maintenance, or recurrence therapy (platinum-resistant disease) 
    • for stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
    • for complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease)
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease)
    • completing prior chemotherapy  
  • As an NCCN preferred adjuvant therapy in combination with carboplatin and paclitaxel for pathologic stage II-IV disease
  • For platinum-sensitive persistent disease or recurrence (except for  immediate treatment of biochemical relapse) for the following indications in combination with:
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 

    • in individuals with complete remission and relapse ≥6 months after completing prior chemotherapy​

    • carboplatin and gemcitabine (preferred)
    • carboplatin and paclitaxel (preferred)
    • carboplatin and liposomal doxorubicin (preferred)  ​ 

  • As NCCN preferred​ therapy for platinum-resistant persistent disease or recurrence in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan (except for  immediate treatment of biochemical relapse) 

  • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy​
  • for progression on primary, maintenance, or recurrence therapy
  • stable or persistent disease (if not on maintenance therapy)
  • for complete remission and relapse <6 months after completing chemotherapy

Malignant Sex Cord-Stromal Tumors


  • As a single agent for clinical relapse in individuals with stage II-IV disease  

Clear Cell Carcinoma


  • Maintenance therapy in combination with olaparib for stage II-IV clear cell carcinoma with a germline or somatic BRCA1/2 mutation if complete response (CR) or partial response (PR) to primary therapy including bevacizumab  ​
  • As an NCCN preferred therapy for platinum-resistant persistent disease or recurrence in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan except for  immediate treatment of biochemical relapse

  • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy
  • for progression on primary, maintenance, or recurrence therapy
  • stable or persistent disease (if not on maintenance therapy)
  • for complete remission and relapse <6 months after completing chemotherapy 
  • For platinum-sensitive persistent disease or recurrence except for  immediate treatment of biochemical relapse 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • in individuals with complete remission and relapse ≥6 months after completing prior chemotherapy
    • in combination with: 
      • carboplatin and gemcitabine (NCCN-preferred)
      • carboplatin and paclitaxel (NCCN-preferred​) 
      • carboplatin and liposomal doxorubicin (preferred) 
  • Targeted therapy in combination with niraparib in platinum-sensitive persistent disease or recurrence except for  immediate treatment of biochemical relapse
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy
  • As NCCN preferred​​ adjuvant therapy​​ in combination with carboplatin and paclitaxel for pathologic stage II-IV disease
  • As NCCN preferred​ targeted therapy as a single agent for persistent disease or recurrence
    • for progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
    • for stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
    • for complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease)
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease)  
  • C​ therapy for rising CA-125 levels or clinical relapse in individuals who have received no prior chemotherapy in combination with paclitaxel and carboplatin  

Grade 1 Endometrioid Carcinoma 


  • As an NCCN preferred​ therapy for platinum-resistant persistent disease or recurrence in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan except for  immediate treatment of biochemical relapse
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy​
    • for progression on primary, maintenance, or recurrence therapy
    • stable or persistent disease (if not on maintenance therapy)
    • for complete remission and relapse <6 months after completing chemotherapy
  • As an NCCN preferred​ targeted therapy as a single agent for persistent disease or recurrence except for  immediate treatment of biochemical relapse
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy​
    • for progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
    • for stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
    • for complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease)
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease) 
  • As an NCCN preferred​ adjuvant therapy in combination with carboplatin and paclitaxel for pathologic stage II-IV, grade 1 endometrioid carcinoma ​ 
  • Targeted therapy in combination with niraparib in platinum-sensitive persistent disease or recurrence (except for  immediate treatment of biochemical relapse) 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse after ≥6 months after completing prior chemotherapy
  • For platinum-sensitive persistent disease or recurrence  as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy or in individuals with complete remission and relapse ≥6 months after completing prior chemotherapy (except for  immediate treatment of biochemical relapse) ​  in combination with 
    • carboplatin and gemcitabine (NCCN-preferred)
    • carboplatin and paclitaxel (NCCN-preferred
    • carboplatin and liposomal doxorubicin (NCCN-preferred​)​ 

Low-Grade Serous Carcinoma/Ovarian Borderline Epithelial Tumors (Low Malignant Potential) with Invasive Implants

 

  • As an NCCN preferred​ therapy for platinum-resistant persistent disease or recurrence in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan except for  immediate treatment of biochemical relapse
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for progression on primary, maintenance, or recurrence therapy 
    • stable or persistent disease (if not on maintenance therapy) 
    • for complete remission and relapse <6 months after completing chemotherapy  
  • For platinum-sensitive persistent disease or recurrence (except for  immediate treatment of biochemical relapse) as immediate treatment for serially rising CA-125 or  in individuals that previously received chemotherapy​ in individuals with complete remission and relapse ≥6 months after completing prior chemotherapy in combination with:
    • carboplatin and gemcitabine (preferred)
    • carboplatin and paclitaxel (preferred)
    • carboplatin and liposomal doxorubicin (preferred) 
  • As NCCN preferred​ treatment for rising CA-125 levels or clinical relapse in individuals who have received no prior chemotherapy in combination with paclitaxel and carboplatin 
  • As NCCN preferred​​ targeted therapy as a single agent for persistent disease or recurrence (except for  immediate treatment of biochemical relapse): 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy
    • for progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
    • for stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
    • for complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease)
  • For radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease)  ​​
  • Targeted therapy in combination with niraparib in platinum-sensitive persistent disease or recurrence (except for  immediate treatment of biochemical relapse)
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy 
  • As NCCN preferred​ adjuvant therapy in combination with carboplatin and paclitaxel for pathologic stage II-IV low-grade serous carcinoma or borderline epithelial tumors with invasive implants 

Grade 1 Endometrioid Carcinoma, Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer 


  • As an NCCN preferred​ for rising CA-125 levels or clinical relapse in individuals who have received no prior chemotherapy in combination with paclitaxel and carboplatin 

Mucinous Carcinoma

 

  • Targeted therapy in combination with niraparib in platinum-sensitive persistent disease or recurrence except for  immediate treatment of biochemical relapse:​
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse after ≥6 months after completing prior chemotherapy 
  • As NCCN preferred​ therapy for rising CA-125 levels or clinical relapse in individuals who have received no prior chemotherapy in combination with paclitaxel and carboplatin 
  • For platinum-sensitive persistent disease or recurrence except for  immediate treatment of biochemical relapse 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy ​
    • in individuals with complete remission and relapse ≥6 months after completing prior chemotherapy
    •  in combination with 
      • carboplatin and gemcitabine (NCCN-preferred)
      • carboplatin and paclitaxel (NCCN-preferred) 
      • carboplatin and liposomal doxorubicin (NCCN-preferred) ​ 
  • As NCCN preferred adjuvant treatment for pathologic stage II-IV disease in combination with carboplatin and paclitaxel
  • As NCCN preferred​ targeted therapy as a single agent for persistent disease or recurrence except for  immediate treatment of biochemical relapse 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
    • for stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
    • for complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease)
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease)

  • As NCCN preferred​ therapy for platinum-resistant persistent disease or recurrence in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan except for  immediate treatment of biochemical relapse
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for progression on primary, maintenance, or recurrence therapy
    • stable or persistent disease (if not on maintenance therapy)
    • for complete remission and relapse <6 months after completing chemotherapy
  • Maintenance therapy as a single agent if used previously as part of combination therapy for individuals with partial or complete response following recurrence therapy with chemotherapy plus bevacizumab for platinum-sensitive disease  ​​ 

Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

 

  • In combination with carboplatin and paclitaxel, followed by bevacizumab or related biosimilar as a single agent, for stage III or IV disease following initial surgical resection 
  • In combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens 
  • In combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by MVASI as a single agent, for platinum sensitive recurrent disease​ 
  • ​​​In individuals who have malignant sex cord-stromal tumors (stage II-IV) as therapy for clinical relapse, as a single agent ​ 
  • Treatment for platinum-sensitive persistent disease or recurrence as immediate treatment for serially rising CA-125 or in individuals with complete remission and relapse ≥6 months after completing prior chemotherapy (except for  immediate treatment of biochemical relapse) in combination with: 

  • carboplatin and gemcitabine (NCCN-preferred)
  • carboplatin and paclitaxel (NCCN-preferred)
  • carboplatin and liposomal doxorubicin (NCCN-preferred) 
  • As NCCN preferred​​ therapy for platinum-resistant persistent disease or recurrence in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan except for  immediate treatment of biochemical relapse
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy 
    • for progression on primary, maintenance, or recurrence therapy
    • stable or persistent disease (if not on maintenance therapy)
    • for complete remission and relapse <6 months after completing chemotherapy
  • As primary adjuvant therapy for pathologic stage II-IV disease​ (NCCN preferred​​ therapy) in combination with paclitaxel and carboplatin   

  • Maintenance therapy for stage II-IV high-grade serous or grade 2/3 endometrioid carcinoma if complete response (CR) or partial response (PR) to primary therapy including bevacizumab 
    • as a single agent in individuals BRCA1/2 wild-type or unknown and HR proficient or status unknown 
    • in combination with olaparib in individuals BRCA1/2 wild-type or unknown and HR deficient  
    • in combination with olaparib in individuals with a germline or somatic BRCA1/2 mutation 
  • As NCCN preferred targeted therapy as a single agent for persistent disease or recurrence except for  immediate treatment of biochemical relapse 
    • as immediate treatment for serially rising CA-125 in individuals that previously received chemotherapy​
    • for progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
    • for stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
    • for complete remission and relapse <6 months after completing chemotherapy (platinum-resistant disease)
    • for radiographic and/or clinical relapse in individuals with previous complete remission and relapse ≥6 months after completing prior chemotherapy (platinum-sensitive disease) 
  • As NCCN preferred​ therapy in combination with paclitaxel and carboplatin for individuals who are poor surgical candidates or have a low likelihood of optimal cytoreduction as: 
    • neoadjuvant therapy
    • continued treatment for stable disease following neoadjuvant therapy
    • adjuvant therapy following interval debulking surgery (IDS) in individuals with response or stable disease to neoadjuvant therapy​
SOFT TISSUE SARCOMA
  • In individuals with angiosarcoma as a single agent
  • In individuals with solitary fibrous tumor or hemangiopericytoma in combination with temozolomide, as NCCN-preferred therapy

UTERINE CANCER/ENDOMETRIAL CANCER
  • As a single agent therapy for recurrent or metastatic disease that has progressed on prior cytotoxic chemotherapy
  • In combination with carboplatin and paclitaxel for advanced and recurrent disease only 
    • ​for disseminated metastases
    • with sequential external beam radiation therapy (EBRT) and with or without brachytherapy for locoregional recurrence in individuals with no prior RT to site of recurrence, or previous brachytherapy only
    • after surgical exploration, with sequential EBRT for locoregional recurrence in individuals with disease confined to the vagina or paravaginal soft tissue, or in pelvic, para-aortic or common iliac lymph nodes
    • after surgical exploration, with or without sequential EBRT for locoregional recurrence in individuals with upper abdominal or peritoneal disease
    • with or without sequential palliative EBRT or brachytherapy for locoregional recurrence in individuals who have received prior EBRT to site of recurrence 
  • ​Primary treatment in combination with carboplatin and paclitaxel for advanced and recurrent disease only:
    • ​with sequential external beam radiation therapy (EBRT) and brachytherapy for a disease that is not suitable for primary surgery in individuals with suspected or gross cervical involvement
    • may be considered preoperatively for individuals presenting with abdominal/pelvic confined disease that is suitable for primary surgery
    • with sequential EBRT and with or without brachytherapy for a locoregional extrauterine disease that is not suitable for primary surgery
    • with or without EBRT and/or stereotactic body radiation therapy for distant metastases that are suitable for primary surgery
    • for distant metastases that are not suitable for primary surgery  
  • Adjuvant treatment for surgically staged individuals​ in combination with paclitaxel and bevacizumab with or without EBRT and with or without vaginal brachytherapy for stage III-IV disease (for advanced and recurrent disease only) 
VULVAR CANCER

In combination with cisplatin and paclitaxel (NCCN-preferred regimen):
  • as additional treatment for unresectable locally advanced disease (larger T2, T3) clinically positive for residual tumor at the primary site and/or nodes
  • as additional treatment for locally advanced disease (larger T2, T3) with positive margins following resection
  • as primary treatment for metastatic disease beyond the pelvis (any T, any N, M1 beyond pelvis) ​
  • for isolated groin/pelvic inguinofemoral/pelvic lymph node recurrence if prior external beam radiation therapy (EBRT)
  • for clinical nodal or distant recurrence with multiple pelvic nodes, distant metastasis, or prior pelvic EBRT​

In accordance with the Centers for Medicare and Medicaid Services (CMS) and in addition to the indications above, paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane® for injectable suspension), as a part of anti-cancer chemotherapy regimen, are covered for the following Micromedex Category IIb indications:

  • Malignant mesothelioma of pleura, Unresectable disease, first-line therapy, in combination with pemetrexed and cisplatin
  • Metastatic breast cancer, HER2-negative, as first-line therapy, in combination with paclitaxel
  • Metastatic breast cancer, HER2-negative, as second-line therapy in combination with other chemotherapy
  • Metastatic breast cancer, In combination with capecitabine in patients previously treated with an anthracycline and a taxane
  • Metastatic colorectal cancer, First-line therapy, in combination with oxaliplatin and capecitabine
  • Metastatic colorectal cancer, In previously untreated elderly patients, ineligible for oxaliplatin- or irinotecan-based chemotherapy
  • Nonsquamous non-small cell lung cancer, Stage IIIB/IV, continuation maintenance therapy as a single-agent following platinum-based, first-line therapy
  • Nonsquamous non-small cell lung cancer, Stage IIIB/IV, first-line therapy in combination with pemetrexed and CARBOplatin
NOT MEDICALLY NECESSARY

For individuals receiving their first course of bevacizumab, use of the non-preferred reference product bevacizumab (Avastin®) or any non-preferred biosimilar, is considered not medically necessary and, therefore, not covered unless the individual has documented contraindication(s) or intolerance(s) to the Company designated preferred products, since they are more costly than the preferred products that are at least as likely to produce equivalent therapeutic results for that individual's illness. 

EXPERIMENTAL/INVESTIGATIONAL

All other uses of bevacizumab and related biosimilars are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

Refer to Attachment A for dosing and frequency requirements for bevacizumab and related biosimilars.

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of bevacizumab and related biosimilars. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (ie, published peer-reviewed literature) in order to request coverage for an amount of bevacizumab and related biosimilars outside of the Dosing and Frequency Requirements listed in this Policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for bevacizumab and related biosimilars.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of bevacizumab and related biosimilars is requested outside of the Dosing and Frequency Guidelines listed in this Policy, the prescribing professional provider must supply documentation (ie, published peer-reviewed literature) to the Company that supports this request.

Guidelines

There is no Medicare coverage criteria addressing the use of bevacizumab and related biosimilars for other indications; therefore, the Company policy is applicable.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, bevacizumab and related biosimilars are covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria, dosing and frequency requirements, and the precertification/preapproval requirements listed in this medical policy are met.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when bevacizumab and related biosimilars are covered under a member's medical benefit (Part B benefit). It does not address instances when bevacizumab and related biosimilars are covered under a member’s pharmacy benefit (Part D benefit).

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The ECOG has developed the ECOG Performance Status; it was originally published in 1982 in the American Journal of Clinical Oncology*. ECOG states, "These scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. They are included here for health care professionals to access."

ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead
*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

PD-L1 IHC 22C3 pharmDx TEST​

PD-L1 IHC 22C3 pharmDx is a qualitative immunohistochemical assay using monoclonal mouse anti-PD-L1, Clone 22C3 intended for use in the detection of PD-L1 protein in formalin-fixed, paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC), gastric or gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma (ESCC), cervical cancer, urothelial carcinoma and head and neck squamous cell carcinoma (HNSCC) tissues using EnVision FLEX visualization system on Autostainer Link 48. PD-L1 protein expression in NSCLC is determined by using Tumor Proportion Score (TPS), which is the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. PD-L1 protein expression in gastric or GEJ adenocarcinoma, ESCC, cervical cancer, urothelial carcinoma and HNSCC is determined by using Combined Positive Score (CPS), which is the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.​

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The initial approval for the use of bevacizumab was granted by the FDA on February 26, 2004. Supplemental approvals have since been issued. The safety, effectiveness, and pharmacokinetic profile of bevacizumab in the pediatric population have not been established.

The FDA has issued subsequent approvals for biosimilar products.

Description

Bevacizumab and related biosimilars are recombinant humanized monoclonal IgG1 antibodies that work by binding to and inhibiting the action of vascular endothelial growth factor (VEGF). VEGF is a substance that binds to certain cells to stimulate new blood vessel formation (angiogenesis). When VEGF is bound to bevacizumab and related biosimilars, it cannot stimulate the formation and growth of new blood vessels. Bevacizumab and related biosimilars are thought to enhance the effects of chemotherapy.

The US Food and Drug Administration (FDA) has granted approval for the use of bevacizumab and related biosimilars for the following indications:
  • In individuals who have metastatic carcinoma of the colon or rectum, as first- or second-line treatment, in combination with intravenous 5-fluorouracil--based chemotherapy
  • In individuals who have metastatic carcinoma of the colon or rectum, as a second-line treatment in patients who have progressed on a first-line bevacizumab regimen, in combination with fluoropyrimidine-, irinotecan-, or fluoropyrimidine-oxaliplatin--based chemotherapy
  • In individuals who have unresectable, locally advanced, recurrent, or metastatic non-squamous non-small cell lung cancer, as first-line treatment in combination with paclitaxel (Taxol®) and carboplatin (Paraplatin®)
  • In individuals who have recurrent glioblastoma, as a single agent
  • In individuals who have metastatic renal cell carcinoma, in combination with interferon alfa
  • In individuals who have persistent, recurrent, or metastatic carcinoma of the cervix, in combination with paclitaxel and cisplatin or paclitaxel and topotecan
  • In individuals who have stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection, in combination with carboplatin and paclitaxel, followed by bevacizumab as a single agent.
  • In individuals who have platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan.
  • In individuals who have platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer when given either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine, followed by bevacizumab as a single agent.
  • In individuals with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy, in combination with atezolizumab (Tecentriq)​
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

In 2008, the FDA gave accelerated approval for the treatment of metastatic breast cancer. However in 2011, the FDA withdrew this indication, since further studies showed only a small delay in tumor growth compared to earlier trials, no increase in overall survival, and an increase in the incidence of serious adverse events. Considering all information from these studies, the FDA concluded that the risks of this drug outweighed its benefits in the treatment of patients with metastatic breast cancer. Although this indication was withdrawn from the FDA, drug compendia still support the use of bevacizumab for the treatment of metastatic breast cancer.

References

American Hospital Formulary Service (AHFS). Bevacizumab (Avastin®). Drug Information 2021. [Lexicomp Online Web site]. 02/26/21. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 23, 2021. 

Bevacizumab (Avastin®) labeling. Genentech, Inc., South San Francisco, CA. 12/2021. Available at: https://www.avastin-hcp.com/ . Accessed January 02, 2022

Eastern Cooperative Oncology Group (ECOG). ECOG performance status. Available at: http://ecog-acrin.org/resources/ecog-performance-status . Accessed November 23, 2021. 

Elsevier’s Clinical Pharmacology Compendium. Bevacizumab (Avastin®), bevacizumab-awwb (Mvasi™)bevacizumab-bvzr (Zirabev™). 11/18/2021. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/monograph/2709?n=Avastin [via subscription only]. Accessed November 23, 2021. 

Lexi-Drugs Compendium. bevacizumab (Avastin). 11/30/2021. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 23, 2021. 

Mvasi (bevacizumab-awwb) labeling. Amgen Inc., Thousand Oaks, CA. 11/2021. Available at: https://www.mvasi.com/hcp. Accessed November 18, 2021. 

National Cancer Institute (NCI). Ovarian epithelial, fallopian tube, and primary peritoneal cancer treatment (PDQ®). Health professional version. ​05/20/2021. [NCI Web site]. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/HealthProfessional/page1 . Accessed November 23, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Breast cancer. v.1.2022. [NCCN Web site]. 11/24/2021. Available at: http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed November 18, 2021

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Central nervous system cancers. v.2.2021. [NCCN Web site]. 09/08/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf​. Accessed November 18, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Cervical cancer. v.1.2022. [NCCN Web site]. 10/26/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf . Accessed November 18, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Colon cancer. v.3.2021. [NCCN Web site]. 09/10/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf . Accessed November 18, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Hepatobiliary cancers. v.5.2021. [NCCN Web site]. 09/21/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf . Accessed November 18, 2021. ​​​​​

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Kidney cancer. v.4.2022. [NCCN Web site]. 12/21/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed January 02, 2022.​​​​​

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Malignant Pleural Mesothelioma. v.1.2022. [NCCN Web site]. 12/22/2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf​ . Accessed January 02, 2022. ​​​​​

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Non-small cell lung cancer. v.1.2022. [NCCN Web site]. 12/07/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf . Accessed January 02, 2022​. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Ovarian cancer, including fallopian tube cancer and primary peritoneal cancer. v.3.2021. [NCCN Web site]. 09/09/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf . Accessed  November 18, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Rectal cancer. v.2.2021. [NCCN Web site]. 09/10/2021​. Available at: https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf . Accessed November 18, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Small bowel adenocarcinoma. v.2.2021. [NCCN Web site]. 09/10/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/small_bowel.pdf . Accessed November 18, 2021. ​​​​​

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Soft Tissue Sarcoma. v.2.2021. [NCCN Web site]. 04/28/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf​ . Accessed November 18, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Uterine Neoplasms. v.1.2022. [NCCN Web site]. 11/04/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf . Accessed November 18, 2021. 

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Vulvar cancer (Squamous cell carcinoma). v.1.2022. [NCCN Web site]. 10/07/2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/vulvar.pdf . Accessed November 18, 2021. ​​​​​

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium™. Bevacizumab (Avastin®), bevacizumab-awwb (Mvasi™)bevacizumab-bvzr (Zirabev™). 2021. [NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed November 18, 2021. 

Pope WB, Lai A, Nghiemphu P, et al. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology. 2006;66(8):1258-1260.

Salah Uddin ABM, Jarmi T. Neurologic Manifestations of Glioblastoma multiforme. [eMedicine Web site]. 11/07/2021. Available at: http://emedicine.medscape.com/article/1156220-overview. Accessed November 23, 2021. 

Truven Health Analytics. Micromedex® DrugDex® Compendium. Bevacizumab (Avastin®), bevacizumab-awwb (Mvasi™)bevacizumab-bvzr (Zirabev™). 11/06/2021. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/ [via subscription only]. Accessed November 23, 2021. 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Avastin (bevacizumab). Package insert. [FDA Web site]. 12/09/2020. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed November 18, 2021

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Mvasi™(bevacizumab-awwb). Package insert. [FDA Web site]. 11/15/2021. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761028 . Accessed November 18, 2021. 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. bevacizumab-bvzr (Zirabev™). Package insert. [FDA Web site]. 02/09/2021. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed November 18, 2021. ​

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Postmarket drug safety information for patients and providers. Questions and answers about avastin. 12/16/2010. Available at: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm237095.htm . Accessed November 18, 2021. 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. PD-L1 IHC 22C3 pharmDx. 07/29/2019. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf15/p150013b.pdf. Accessed January 02, 2022. 

Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13(4):1253-1259.

Zirabev (bevacizumab-bvzr) labeling. Pfizer Inc., NY, NY. 02/2021. Available at: https://www.zirabev.com/ . Accessed November 18, 2021. ​​

Coding

CPT Procedure Code Number(s)
N/A

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)

​​C17.0 Malignant neoplasm of duodenum

C17.1 Malignant neoplasm of jejunum

C17.2 Malignant neoplasm of ileum

C17.3 Meckel's diverticulum, malignant

C17.8 Malignant neoplasm of overlapping sites of small intestine

C17.9 Malignant neoplasm of small intestine, unspecified

C18.0 Malignant neoplasm of cecum
C18.1 Malignant neoplasm of appendix
C18.2 Malignant neoplasm of ascending colon
C18.3 Malignant neoplasm of hepatic flexure
C18.4 Malignant neoplasm of transverse colon
C18.5 Malignant neoplasm of splenic flexure
C18.6 Malignant neoplasm of descending colon
C18.7 Malignant neoplasm of sigmoid colon
C18.8 Malignant neoplasm of overlapping sites of colon
C18.9 Malignant neoplasm of colon, unspecified
C19 Malignant neoplasm of rectosigmoid junction
C20 Malignant neoplasm of rectum
C21.8 Malignant neoplasm of overlapping sites of rectum, anus and anal canal
C22.0 Liver cell carcinoma
C22.1 Intrahepatic bile duct carcinoma
C22.2 Hepatoblastoma
C22.3 Angiosarcoma of liver
C22.4 Other sarcomas of liver
C22.7 Other specified carcinomas of liver
C22.8 Malignant neoplasm of liver, primary, unspecified as to type
C22.9 Malignant neoplasm of liver, not specified as primary or secondary
C24.1 Malignant neoplasm of ampulla of Vater

C33 Malignant neoplasm of trachea
C34.00 Malignant neoplasm of unspecified main bronchus
C34.01 Malignant neoplasm of right main bronchus
C34.02 Malignant neoplasm of left main bronchus
C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11 Malignant neoplasm of upper lobe, right bronchus or lung
C34.12 Malignant neoplasm of upper lobe, left bronchus or lung
C34.2 Malignant neoplasm of middle lobe, bronchus or lung
C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.31 Malignant neoplasm of lower lobe, right bronchus or lung
C34.32 Malignant neoplasm of lower lobe, left bronchus or lung
C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung
C34.81 Malignant neoplasm of overlapping sites of right bronchus and lung
C34.82 Malignant neoplasm of overlapping sites of left bronchus and lung
C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung
C34.91 Malignant neoplasm of unspecified part of right bronchus or lung
C34.92 Malignant neoplasm of unspecified part of left bronchus or lung
C45.0 Mesothelioma of pleura

C48.0 Malignant neoplasm of retroperitoneum
C48.1 Malignant neoplasm of specified parts of peritoneum
C48.2 Malignant neoplasm of peritoneum, unspecified
C48.8 Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum
C49.0 Malignant neoplasm of connective and soft tissue of head, face and neck
C49.3   Malignant neoplasm of connective and soft tissue of thorax

C49.4   Malignant neoplasm of connective and soft tissue of abdomen

C49.5   Malignant neoplasm of connective and soft tissue of pelvis

C49.8   Malignant neoplasm of overlapping sites of connective and soft tissue

C49.9   Malignant neoplasm of connective and soft tissue, unspecified

C49.10 Malignant neoplasm of connective and soft tissue of unspecified upper limb, including shoulder
C49.11 Malignant neoplasm of connective and soft tissue of right upper limb, including shoulder
C49.12 Malignant neoplasm of connective and soft tissue of left upper limb, including shoulder
C49.20 Malignant neoplasm of connective and soft tissue of unspecified lower limb, including hip
C49.21 Malignant neoplasm of connective and soft tissue of right lower limb, including hip
C49.22 Malignant neoplasm of connective and soft tissue of left lower limb, including hip
C49.3 Malignant neoplasm of connective and soft tissue of thorax
C49.4 Malignant neoplasm of connective and soft tissue of abdomen
C49.5 Malignant neoplasm of connective and soft tissue of pelvis
C49.6 Malignant neoplasm of connective and soft tissue of trunk, unspecified
C49.8 Malignant neoplasm of overlapping sites of connective and soft tissue
C49.9 Malignant neoplasm of connective and soft tissue, unspecified
C50.011 Malignant neoplasm of nipple and areola, right female breast
C50.012 Malignant neoplasm of nipple and areola, left female breast
C50.019 Malignant neoplasm of nipple and areola, unspecified female breast
C50.021 Malignant neoplasm of nipple and areola, right male breast
C50.022 Malignant neoplasm of nipple and areola, left male breast
C50.029 Malignant neoplasm of nipple and areola, unspecified male breast
C50.111 Malignant neoplasm of central portion of right female breast
C50.112 Malignant neoplasm of central portion of left female breast
C50.119 Malignant neoplasm of central portion of unspecified female breast
C50.121 Malignant neoplasm of central portion of right male breast
C50.122 Malignant neoplasm of central portion of left male breast
C50.129 Malignant neoplasm of central portion of unspecified male breast
C50.211 Malignant neoplasm of upper-inner quadrant of right female breast
C50.212 Malignant neoplasm of upper-inner quadrant of left female breast
C50.219 Malignant neoplasm of upper-inner quadrant of unspecified female breast
C50.221 Malignant neoplasm of upper-inner quadrant of right male breast
C50.222 Malignant neoplasm of upper-inner quadrant of left male breast
C50.229 Malignant neoplasm of upper-inner quadrant of unspecified male breast
C50.311 Malignant neoplasm of lower-inner quadrant of right female breast
C50.312 Malignant neoplasm of lower-inner quadrant of left female breast
C50.319 Malignant neoplasm of lower-inner quadrant of unspecified female breast
C50.321 Malignant neoplasm of lower-inner quadrant of right male breast
C50.322 Malignant neoplasm of lower-inner quadrant of left male breast
C50.329 Malignant neoplasm of lower-inner quadrant of unspecified male breast
C50.411 Malignant neoplasm of upper-outer quadrant of right female breast
C50.412 Malignant neoplasm of upper-outer quadrant of left female breast
C50.419 Malignant neoplasm of upper-outer quadrant of unspecified female breast
C50.421 Malignant neoplasm of upper-outer quadrant of right male breast
C50.422 Malignant neoplasm of upper-outer quadrant of left male breast
C50.429 Malignant neoplasm of upper-outer quadrant of unspecified male breast
C50.511 Malignant neoplasm of lower-outer quadrant of right female breast
C50.512 Malignant neoplasm of lower-outer quadrant of left female breast
C50.519 Malignant neoplasm of lower-outer quadrant of unspecified female breast
C50.521 Malignant neoplasm of lower-outer quadrant of right male breast
C50.522 Malignant neoplasm of lower-outer quadrant of left male breast
C50.529 Malignant neoplasm of lower-outer quadrant of unspecified male breast
C50.611 Malignant neoplasm of axillary tail of right female breast
C50.612 Malignant neoplasm of axillary tail of left female breast
C50.619 Malignant neoplasm of axillary tail of unspecified female breast
C50.621 Malignant neoplasm of axillary tail of right male breast
C50.622 Malignant neoplasm of axillary tail of left male breast
C50.629 Malignant neoplasm of axillary tail of unspecified male breast
C50.811 Malignant neoplasm of overlapping sites of right female breast
C50.812 Malignant neoplasm of overlapping sites of left female breast
C50.819 Malignant neoplasm of overlapping sites of unspecified female breast
C50.821 Malignant neoplasm of overlapping sites of right male breast
C50.822 Malignant neoplasm of overlapping sites of left male breast
C50.829 Malignant neoplasm of overlapping sites of unspecified male breast
C50.911 Malignant neoplasm of unspecified site of right female breast
C50.912 Malignant neoplasm of unspecified site of left female breast
C50.919 Malignant neoplasm of unspecified site of unspecified female breast
C50.921 Malignant neoplasm of unspecified site of right male breast
C50.922 Malignant neoplasm of unspecified site of left male breast
C50.929 Malignant neoplasm of unspecified site of unspecified male breast
C51.0 Malignant neoplasm of labium majus
C51.1 Malignant neoplasm of labium minus
C51.2 Malignant neoplasm of clitoris
C51.8 Malignant neoplasm of overlapping sites of vulva
C51.9 Malignant neoplasm of vulva, unspecified
C51.8 Malignant neoplasm of overlapping sites of vulva
C51.9 Malignant neoplasm of vulva, unspecified
C53.0 Malignant neoplasm of endocervix
C53.1 Malignant neoplasm of exocervix
C53.8 Malignant neoplasm of overlapping sites of cervix uteri
C53.9 Malignant neoplasm of cervix uteri, unspecified
C54.0 Malignant neoplasm of isthmus uteri
C54.1 Malignant neoplasm of endometrium
C54.2 Malignant neoplasm of myometrium
C54.3 Malignant neoplasm of fundus uteri
C54.8 Malignant neoplasm of overlapping sites of corpus uteri
C54.9 Malignant neoplasm of corpus uteri, unspecified
C55 Malignant neoplasm of uterus, part unspecified
C56.1 Malignant neoplasm of right ovary
C56.2 Malignant neoplasm of left ovary
C56.3 Malignant neoplasm of bilateral ovaries
C56.9 Malignant neoplasm of unspecified ovary
C57.00 Malignant neoplasm of unspecified fallopian tube
C57.01 Malignant neoplasm of right fallopian tube
C57.02 Malignant neoplasm of left fallopian tube
C57.10 Malignant neoplasm of unspecified broad ligament
C57.11 Malignant neoplasm of right broad ligament
C57.12 Malignant neoplasm of left broad ligament
C57.20 Malignant neoplasm of unspecified round ligament
C57.21 Malignant neoplasm of right round ligament
C57.22 Malignant neoplasm of left round ligament
C57.3 Malignant neoplasm of parametrium
C57.4 Malignant neoplasm of uterine adnexa, unspecified
C57.7 Malignant neoplasm of other specified female genital organs
C57.8 Malignant neoplasm of overlapping sites of female genital organs
C64.1 Malignant neoplasm of right kidney, except renal pelvis
C64.2 Malignant neoplasm of left kidney, except renal pelvis
C64.9 Malignant neoplasm of unspecified kidney, except renal pelvis
C65.1 Malignant neoplasm of right renal pelvis
C65.2 Malignant neoplasm of left renal pelvis
C65.9 Malignant neoplasm of unspecified renal pelvis
C70.0 Malignant neoplasm of cerebral meninges
C70.1 Malignant neoplasm of spinal meninges
C70.9 Malignant neoplasm of meninges, unspecified
C71.0 Malignant neoplasm of cerebrum, except lobes and ventricles
C71.1 Malignant neoplasm of frontal lobe
C71.2 Malignant neoplasm of temporal lobe
C71.3 Malignant neoplasm of parietal lobe
C71.4 Malignant neoplasm of occipital lobe
C71.5 Malignant neoplasm of cerebral ventricle
C71.6 Malignant neoplasm of cerebellum
C71.7 Malignant neoplasm of brain stem
C71.8 Malignant neoplasm of overlapping sites of brain
C71.9 Malignant neoplasm of brain, unspecified
C72.0 Malignant neoplasm of spinal cord
C72.9   Malignant neoplasm of central nervous system, unspecified
C78.00 Secondary malignant neoplasm of unspecified lung
C78.01 Secondary malignant neoplasm of right lung
C78.02 Secondary malignant neoplasm of left lung
C78.6 Secondary malignant neoplasm of retroperitoneum and peritoneum
C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct
C79.31 Secondary malignant neoplasm of brain
C83.30 Diffuse large B-cell lymphoma, unspecified site

C83.39 Diffuse large B-cell lymphoma, extranodal and solid organ sites

C83.80 Other non-follicular lymphoma, unspecified site

C83.89 Other non-follicular lymphoma, extranodal and solid organ sites

C85.89 Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites

C85.99 Non-Hodgkin lymphoma, unspecified, extranodal and solid organ sites

D39.10 Neoplasm of uncertain behavior of unspecified ovary

D39.11 Neoplasm of uncertain behavior of right ovary

D39.12 Neoplasm of uncertain behavior of left ovary

D39.8   Neoplasm of uncertain behavior of other specified female genital organs

D39.9   Neoplasm of uncertain behavior of female genital organ, unspecified​


HCPCS Level II Code Number(s)

C9257 Injection, bevacizumab, 0.25 mg


J9035 Injection, bevacizumab, 10 mg

Q5107 Injection, bevacizumab-awwb, biosimilar, (mvasi), 10 mg

Q5118 Injection, bevacizumab-bvzr, biosimilar, (Zirabev), 10 mg


THE FOLLOWING CODES REPRESENT BEVACIZUMAB-MALY, (ALYMSYS):


C9142 Injection, bevacizumab-maly, biosimilar, (alymsys), 10 mg

J3590  Unclassified biologics​



Revenue Code Number(s)
N/A



Coding and Billing Requirements

BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).

Policy History

10/1/2022
9/30/2022
MA08.072
Medical Policy Bulletin
Medicare Advantage
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No