Notification



Notification Issue Date:



Policy Attachment

Attachment to Policy # MA08.072e


Attachment:A

Policy #:MA08.072e

Description:Dosing and Frequency Requirements

Title:Bevacizumab (Avastin®) and Related Biosimilars

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.


DOSING AND FREQUENCY REQUIREMENTS FOR BEVACIZUMAB (AVASTIN®) 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 (Avastin®) 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 (Avastin®) 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 (Avastin®) and related biosimilars.

Indication
Dosing and Frequency
AIDS-related Kaposi Sarcoma AIDS-related Kaposi Sarcoma: 15 mg/kg on Day 1 of a 7-day cycle (loading dose), followed by 15 mg/kg Day 1 of a 21-day cycle until disease progression or unacceptable toxicity 57
Breast
carcinoma
invasive
In combination with paclitaxel in individuals with high tumor burden, rapidly progressing disease, and visceral crisis for recurrent or stage IV (M1) human epidermal growth factor receptor 2 (HER2)--negative disease that meets any of the following criteria:
  • Hormone receptor--negative
  • Hormone receptor--positive with visceral crisis or endocrine therapy refractory

10 mg/kg on days 1 and 15 in a 28-day cycle until disease progression or unacceptable toxicity 44, 57, 59
Central
nervous
system
tumors 26, 27, 35, 36, 37, 38

Recurrent glioblastoma with progressive disease following prior therapy, as a single agent: 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity 1, 19, 28, 42, 43, 45, 57, 60, 86

As short-course single agent therapy for management of symptoms driven by RT necrosis, poorly controlled vasogenic edema, or mass effect for any of the following conditions:
  • Adult low-grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma
  • Anaplastic glioma
  • Glioblastoma
  • Adult intracranial and spinal ependymoma (excludes subependymoma)
  • Adult medulloblastoma
  • Primary central nervous system lymphoma
  • Meningiomas
  • Brain Metastases (limited or extensive)
  • Leptomeningeal metastases
  • Metastatic spine tumors
    10 mg/kg every 2 weeks until disease progression or unacceptable toxicity 57, 60, 91, 92

Treatment as a single-agent for disease progression or recurrent adult intracranial and spinal ependymoma (excludes subependymoma) if received prior RT and individuals has any of the following:
  • gross total or subtotal resection
  • localized recurrence
  • evidence of metastasis (brain, spine, or CSF)
    10 mg/kg every 2 weeks until disease progression or unacceptable toxicity 24, 28, 39, 40, 41, 45, 57, 60

Treatment of recurrent disease as a single agent (NCCN-preferred) or in combination with carmustine, lomustine, or temozolomide for anaplastic glioma or glioblastoma
  • As a single agent: 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity 28, 32, 33, 34, 40, 41, 42, 45, 57, 60
  • With carmustine or lomustine: One of the following
    • 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity 57, 60, 89
    • 10 mg/kg on Days 1 and 15 of a 21-day cycle for 2 doses, followed after a 3-week interval by 10 mg/kg every 3 weeks until disease progression or unacceptable toxicity 57, 60, 79, 88, 90
  • With temozolomide: 10 mg/kg every 3 weeks until disease progression or unacceptable toxicity 22, 23, 24, 25, 31, 57, 60

Treatment as single agent for surgically inaccessible recurrent or progressive meningiomas when radiation is not possible: 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity 28, 45, 57, 60, 91, 92
Cervical carcinomaPersistent, recurrent, or metastatic carcinoma of the cervix in combination with paclitaxel and cisplatin or paclitaxel and topotecan: 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity 1, 86

As first-line or second-line therapy as clinically appropriate (if not used previously as first-line) in combination with cisplatin and paclitaxel, paclitaxel and carboplatin, or paclitaxel and topotecan (NCCN-preferred regimens) for local/regional recurrence or Stage IVB or distant metastases: 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity 3, 4, 57, 83, 84
Colon
or
rectal
carcinoma
Colorectal:

Metastatic carcinoma of the colon or rectum, as first- or second-line treatment, in combination with intravenous 5-fluorouracil--based chemotherapy:
  • IFL (irinotecan, fluorouracil, leucovorin): 5 mg/kg every 2 weeks until disease progression or unacceptable toxicity1, 86
  • FOLFOX4 (fluorouracil, leucovorin, oxaliplatin): 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity1, 47, 86

Metastatic carcinoma of the colon or rectum, as a second-line treatment after progression on a first-line bevacizumab (Avastin®) or related biosimilar -- containing regimen, in combination with fluoropyrimidine- irinotecan- or fluoropyrimidine-oxaliplatin--based chemotherapy: 5 mg/kg administered every 2 weeks or 7.5 mg/kg administered every 3 weeks until disease progression or unacceptable toxicity1, 86

For colon or rectal carcinoma as National Comprehensive Cancer Network's (NCCN) preferred anti-angiogenic therapy as primary treatment for individuals with unresectable metachronous metastases and previously received adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months:
  • Irinotecan:
    • 5 mg/kg every 2 weeks until disease progression or unacceptable toxicity 57, 61, 63
    or
    • 7.5 mg/kg IV on the first day of a 21-day cycle until disease progression or unacceptable toxicity 57, 61, 63
  • FOLFIRI (fluorouracil, leucovorin, and irinotecan):
    • 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61, 63, 67, 68, 85

For colon or rectal carcinoma as subsequent therapy for progression of advanced or metastatic disease in combination with one of the following scenarios:
  • FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) regimen for disease previously treated with irinotecan-based therapy without oxaliplatin
  • FOLFOX, CapeOX, or irinotecan and oxaliplatin for individuals previously treated with fluoropyrimidine therapy without irinotecan or oxaliplatin
  • As the NCCN-preferred anti-angiogenic agent in combination with irinotecan or with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen in individuals previously treated with one of the following regimens:
    • fluoropyrimidine therapy without irinotecan or oxaliplatin
    • oxaliplatin-based therapy without irinotecan

mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61, 63, 64, 65, 66

CapeOX (capecitabine and oxaliplatin): 7.5 mg/kg IV on the first day of a 21-day cycle until disease progression or unacceptable toxicity 49, 57, 61, 63, 65, 66, 69, 70

Irinotecan: 5 mg/kg every 2 weeks until disease progression or unacceptable toxicity 57, 61, 63 or 7.5 mg/kg IV on the first day of a 21-day cycle until disease progression or unacceptable toxicity 57, 61, 63

FOLFIRI (fluorouracil, leucovorin, and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61, 63, 67, 68, 85

Irinotecan and oxaliplatin: 7.5 mg/kg every 3 weeks until disease progression or unacceptable toxicity 57, 61, 63


Colon:

For colon carcinoma, as initial treatment for unresectable synchronous liver and/or lung metastases in combination with one of the following regimens:
  • mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61, 64, 65, 66
  • FOLFIRI (fluorouracil, leucovorin, and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61, 67, 68, 85
  • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61
  • CapeOX (capecitabine and oxaliplatin): 7.5 mg/kg IV on the first day of a 21-day cycle until disease progression or unacceptable toxicity 49, 57, 61, 66

For colon carcinoma in combination with any of the following regimens:
  • 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 imminent or existing obstruction
  • for unresectable synchronous 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
    • capecitabine: 7.5 mg/kg on the first day of a 21-day cycle until disease progression or unacceptable toxicity 9, 16, 57, 61
    • mFOLFOX6 (fluorouracil continuous infusion/leucovorin/oxaliplatin): 5 mg/kg on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61, 64, 65, 66
    • FOLFIRI (fluorouracil, leucovorin, and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61, 67, 68, 85
    • CapeOx (capecitabine/oxaliplatin): 7.5 mg/kg on the first day of a 21-day cycle until disease progression or unacceptable toxicity 48, 49, 57, 61, 66, 69, 70
    • FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 61
    • Roswell Park fluorouracil and leucovorin: 5 mg/kg on the first day of a 14-day cycle until disease progression or unacceptable toxicity50, 57, 58, 61, 62
    • Simplified biweekly infusional fluorouracil and leucovorin: 5 mg/kg on the first day of a 14-day cycle until disease progression or unacceptable toxicity50, 57, 61, 62, 68
    • Weekly fluorouracil/leucovorin: 5 mg/kg on the first day of a 14-day cycle until disease progression or unacceptable toxicity17, 18, 50, 57, 62


Rectal:

Therapy in combination with capecitabine or with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), CapeOX (capecitabine and oxaliplatin), FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan), or 5-FU/leucovorin (fluorouracil and leucovorin) regimen for the following conditions:
  • 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
  • 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 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 patients with existing or imminent obstruction
  • as primary treatment for synchronous unresectable metastases of other sites
  • as primary treatment for unresectable metachronous metastases in patients 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
    • Roswell Park fluorouracil and leucovorin: 5 mg/kg on the first day of a 14-day cycle until disease progression or unacceptable toxicity50, 57, 58, 62, 63
    • Weekly fluorouracil/leucovorin: 5 mg/kg on the first day of a 14-day cycle until disease progression or unacceptable toxicity17, 18, 50, 57, 62, 63
    • capecitabine: 7.5 mg/kg on the first day of a 21-day cycle until disease progression or unacceptable toxicity 9, 16, 57, 63
    • mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 63, 64, 65, 66
    • FOLFIRI (fluorouracil, leucovorin, and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 63, 67, 68
    • CapeOx (capecitabine/oxaliplatin): 7.5 mg/kg on the first day of a 21-day cycle until disease progression or unacceptable toxicity 48, 49, 57, 63, 66, 69, 70
    • FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 63
    • Simplified biweekly infusional fluorouracil and leucovorin: 5 mg/kg on the first day of a 14-day cycle until disease progression or unacceptable toxicity50, 57, 61, 62, 68

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): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 63, 67, 68
  • mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 63, 64, 65, 66
  • CapeOx (capecitabine/oxaliplatin): 7.5 mg/kg on the first day of a 21-day cycle until disease progression or unacceptable toxicity 48, 49, 57, 63, 66, 69, 70
  • FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan): 5 mg/kg IV on the first day of a 14-day cycle until disease progression or unacceptable toxicity 57, 63
Kidney
carcinoma
In individuals who have metastatic renal cell carcinoma (mRCC) in combination with interferon alpha: 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity1, 54, 86

In individuals with relapsed or stage IV kidney cancer with one of the following conditions:
  • clear cell histology in combination with interferon alfa-2b as first-line therapy: 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity 8, 54, 57, 73
  • non-clear cell histology as a single agent : 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity 2, 7, 57, 72, 73
  • in combination with erlotinib for non-clear cell histology in selected patients with advanced papillary renal cell carcinoma including hereditary leiomyomatosis and renal cell cancer (HLRCC): 10 mg/kg on Days 1 and 15 of a 28-day cycle until disease progression or unacceptable toxicity 57
  • in combination with everolimus as systemic therapy for non-clear cell histology: 10 mg/kg on Days 1 and 15 of a 28-day cycle until disease progression or unacceptable toxicity 57
Malignant Pleural Mesothelioma In combination with pemetrexed and either cisplatin or carboplatin 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 histology
  • clinical stage IIIB or IV disease or medically inoperable tumors in individuals with performance status (PS) 0-2

15 mg/kg every 21 days for a maximum of 6 cycles with pemetrexed and either cisplatin or carboplatin, followed by 15 mg/kg every 21 days until disease progression or unacceptable toxicity57, 87
Non-
squamous
non-small cell
lung cancer (NSCLC)
In individuals who have unresectable, locally advanced, recurrent, or metastatic NSCLC, as first-line treatment in combination with paclitaxel (Taxol®) and carboplatin (Paraplatin®): 15 mg/kg every 21 days until disease progression or unacceptable toxicity1, 51, 52, 53, 86

Treatment for recurrent, advanced, or metastatic disease** as first-line therapy for PD-L1 expression positive (≥1%) tumors that are EGFR, ALK negative or unknown and no contraindications to the addition of pembrolizumab or atezolizumab and performance status 0-2 in combination with atezolizumab, carboplatin and paclitaxel for nonsquamous cell histology: 15 mg/kg every 21 days until disease progression or unacceptable toxicity 55, 57

Continuation maintenance therapy as a single agent or in combination with atezolizumab for recurrent, advanced or metastatic disease** for PD-L1 expression positive (≥1%) tumors that are EGFR, ALK negative or unknown and no contraindications to the addition of pembrolizumab or atezolizumab in individuals with PS 0-2 who achieve a response or stable disease following first-line therapy with atezolizumab/carboplatin/paclitaxel/bevacizumab for nonsquamous cell histology: 15 mg/kg every 21 days until disease progression or unacceptable toxicity 55, 57

In combination with carboplatin and either paclitaxel or pemetrexed (if contraindications to the addition of pembrolizumab or atezolizumab), or in combination with cisplatin and pemetrexed (if contraindications to the addition of pembrolizumab or atezolizumab), or in combination with atezolizumab, carboplatin and paclitaxel (if no contraindications to the addition of pembrolizumab or atezolizumab) for recurrent, advanced or metastatic disease** in individuals with PS 0 to 1, tumors of nonsquamous cell histology, and no history of recent hemoptysis for one of the following regimens:
  • initial systemic therapy for EGFR, ALK, ROS1, BRAF negative or unknown, and PD-L1 <1% or unknown
  • first-line or subsequent therapy for BRAF V600E-mutation positive tumors
  • subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, osimertinib, or dacomitinib therapy
  • subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, alectinib, or brigatinib therapy
  • subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib or ceritinib therapy
  • subsequent therapy for PD-L1 expression-positive (≥1%) tumors and EGFR, ALK negative or unknown and no prior platinum-doublet chemotherapy
    • With carboplatin and paclitaxel: 15 mg/kg every 21 days for a maximum of 6 cycles 55, 57, 82
    • With carboplatin and pemetrexed: 15 mg/kg every 21 days for a maximum of 4 cycles 55, 57
    • With cisplatin and pemetrexed: 7.5 mg/kg every 21 days for a maximum of 4 cycles 55, 57

Continuation Maintenance therapy for recurrent, advanced, or metastatic disease** in individuals with performance status 0 to 2, tumors 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: 15 mg/kg on the first day of a 21-day cycle until disease progression or unacceptable toxicity 55, 57, 58
  • in combination with pemetrexed (if previously used with a first-line pemetrexed/platinum chemotherapy regimen): 7.5 to 15 mg/kg on the first day of a 21-day cycle until disease progression or unacceptable toxicity 52, 55, 57
  • in combination with atezolizumab (if previously used first-line as part of an atezolizumab/carboplatin/paclitaxel/bevacizumab regimen): 15 mg/kg every 21 days until disease progression or unacceptable toxicity 55, 57

**Excludes coverage 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.
Ovarian
cancer
If platinum-resistant, in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan for persistent disease or recurrence (not including biochemical relapse) in individuals who have received no more than two prior chemotherapy regimens as NCCN-preferred therapy.
  • 10 mg/kg every 2 weeks in combination with weekly doses of either paclitaxel, pegylated liposomal doxorubicin, or topotecan 1
or
  • 15 mg/kg every 3 weeks in combination with topotecan every 3 weeks 1

If platinum-resistant, as a single agent for persistent disease or recurrence (not including biochemical relapse) as NCCN-preferred therapy: 15 mg/kg every 21 days until disease progression or unacceptable toxicity10, 11, 12, 13, 14, 15, 57, 71

In combination with carboplatin and gemcitabine (if platinum-sensitive), followed by bevacizumab (Avastin®) or related biosimilar as a single agent for persistent disease or recurrence (not including biochemical relapse) as NCCN-preferred therapy: 15 mg/kg every 3 weeks when administrated in combination with carboplatin and gemcitabine for 6-10 cycles, followed by bevacizumab (Avastin®) or related biosimilar 15 mg/kg every 3 weeks as a single agent until disease progression or unacceptable toxicity1

In combination with carboplatin and liposomal doxorubicin for persistent disease or recurrence (not including biochemical relapse) if platinum-sensitive, as NCCN-preferred therapy: 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity93

Persistent disease or recurrence, platinum-sensitive disease (not including biochemical relapse) as NCCN-preferred therapy: 15 mg/kg every 3 weeks when administered in combination with carboplatin and paclitaxel for 6-8 cycles, followed by bevacizumab (Avastin®) or related biosimilar 15 mg/kg every 3 weeks as a single agent until disease progression or unacceptable toxicity1

In individuals who have malignant sex cord-stromal tumors (stage II-IV) as therapy for clinical relapse, as a single agent: 15 mg/kg every 21 days until disease progression or unacceptable toxicity57, 71, 74
For the conditions listed below, use either of the following regimens:
  • Bevacizumab 7.5 mg/kg every 3 weeks for 5-6 cycles, with paclitaxel and carboplatin. Continue bevacizumab for up to 12 additional cycles (ICON-7 regimen). 57, 71
or
  • Bevacizumab 15 mg/kg, paclitaxel and carboplatin (bevacizumab started on Cycle 2) every 3 weeks for 6 cycles. Continue bevacizumab for up to 22 cycles (GOG-218 regimen). 57, 71

In combination with carboplatin and paclitaxel, followed by bevacizumab (Avastin®) or related biosimilar as a single agent for one of the following:
  • In individuals who have not received prior chemotherapy and are experiencing rising CA-125 levels or clinical relapse
  • Poor surgical candidates or have low likelihood of optimal cytoreduction as:
    • neoadjuvant therapy
    • continued treatment for stable disease following neoadjuvant therapy

Primary treatment for individuals with incomplete previous surgery and/or staging with Stage II-IV and suspected unresectable residual disease

Primary adjuvant therapy for pathologic Stage II-IV disease with endometroid or serous histology 1

Adjuvant treatment for the following pathologic stages and histology:
  • Stage I-IV disease and carcinosarcoma histology, as NCCN-preferred therapy
  • Stage II-IV disease and clear cell histology
  • Stage II-IV disease and mucinous histology
  • Stage II-IV, grade 1 endometrioid carcinoma
  • Stage II-IV low-grade serous carcinoma or borderline epithelial tumors with invasive implants

Maintenance therapy as a single agent if used previously as part of a combination therapy:
  • Partial or complete remission or stable disease following primary therapy for Stage II-IV disease
  • Partial or complete response following recurrence therapy with bevacizumab for platinum-sensitive disease
Soft
tissue sarcoma
As a single agent for angiosarcoma: 15 mg/kg IV every 21 days until maximal response, disease progression or unacceptable toxicity 57, 75, 77

In combination with temozolomide for the treatment of solitary fibrous tumor or hemangiopericytoma: 5 mg/kg IV on days 8 and 22, repeated at 28-day intervals until disease progression or unacceptable toxicity 57, 75, 76, 77
Uterine/Endometrial Cancer As a single agent for disease that has progressed on prior cytotoxic chemotherapy: 15 mg/kg every 21 days for 6 cycles (adjuvant) or until disease progression or unacceptable toxicity (recurrent or metastatic) 57, 80, 81

In combination with carboplatin and paclitaxel for advanced and recurrent disease: 15 mg/kg IV every 21 days for 6-8 cycles 57
Vulvar Cancer In combination with cisplatin and paclitaxel (NCCN-preferred regimen): 15 mg/kg IV every 21 days until disease progression or unacceptable toxicity 57


References:

1. US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Avastin (bevacizumab). Package insert. [FDA Web site]. 04/03/2019. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed April 23, 2019.

2. Irshad T, Olencki T, Zynger DL, et al. Bevacizumab in metastatic papillary renal cell carcinoma (PRCC). Journal of Clinical Oncology. 2011 ASCO Annual Meeting Abstracts Part 1. Vol 29, No 15_suppl (May 20 Supplement), 2011: e15158.

3. Monk BJ, Sill MW, Burger RA, et al. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74.

4. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Cervical cancer. v.4.2019. [NCCN Web site]. 03/29/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cervical_blocks.pdf . Accessed April 26, 2019.

5. Schrag D, Weiser MR, Goodman KA, et al. Neoadjuvant FOLFOX-bev, without radiation, for locally advanced rectal cancer. J Clin Oncol. 2010;28:15s(suppl; abstr 3511).

6. Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009;27(8):1227-34.

7. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349(5):427-34.

8. Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010;28(13):2137-43.

9. Van Cutsem E, Twelves C, Cassidy J, et al. Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001;19(21):4097-106.

10. Kumaran GC, Jayson GC, Clamp AR. Antiangiogenic drugs in ovarian cancer. Br J Cancer. 2009;100(1):1-7.

11. Burger RA, Sill MW, Monk BJ, et al. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:5165–5171.

12. Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25:5180–5186.

13. Monk BJ, Choi DC, Pugmire G, Burger RA. Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer. Gynecol Oncol. 2005;96(3):902-5.

14. Monk BJ, Han E, Josephs-Cowan CA, Pugmire G, Burger RA. Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer. Gynecol Oncol. 2006;102(2):140-4.
15. Bidus MA, Webb JC, Seidman JD, et al. Sustained response to bevacizumab in refractory well-differentiated ovarian neoplasms. Gynecol Oncol. 2006;102(1):5-7.

16. Van Cutsem E, Rivera F, Berry S, et al.; First BEAT investigators. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009;20(11):1842-7.

17. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355(9209):1041-7.

18. Jäger E, Heike M, Bernhard H, et al. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J Clin Oncol. 1996;14(8):2274-9.

19. Cloughesy TF, Prados MD, Wen PY, et al. A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab alone or in combination with irinotecan on 6-month progression free survival in recurrent, treatment-refractory glioblastoma. Presented at ASCO Annual Meeting. Chicago, IL; 2008. Abstract 2010b.

20. Vredenburgh JJ, Desjardins A, Herndon JE, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007;25:4722-4729.

21. Wagner SA, Desjardins A, Reardon DA, et al. Update on survival from the original phase II trial of bevacizumab and irinotecan in recurrent malignant gliomas. J Clin Oncol. 2008;26:(May 20 suppl; abstr 2021).

22. Van Meir EG, Hadjipanayis CG, Norden AD, et al. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010;60(3):166-93.

23. Zhang W, Qiu XG, Chen BS, et al. Antiangiogenic therapy with bevacizumab in recurrent malignant gliomas: analysis of the response and core pathway aberrations. Chin Med J (Engl). 2009;122(11):1250-4.

24. Green RM, Cloughesy TF, Stupp R, et al. Bevacizumab for recurrent ependymoma. Neurology. 2009;17;73(20):1677-80.

25. Moen MD. Bevacizumab: in previously treated glioblastoma. Drugs. 2010;70(2):181-9.

26. Desjardins A, Reardon DA, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res. 2008;14(21):7068-73.

27. Wick W, Weller M, van den Bent M, Stupp R. Bevacizumab and recurrent malignant gliomas: a European perspective. J Clin Oncol. 2010;28(12):e188-9; author reply e190-2.

28. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733-40.

29. 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):1253-9.

30. de Groot JF, Yung WK. Bevacizumab and irinotecan in the treatment of recurrent malignant gliomas. Cancer J. 2008;14(5):279-85.

31. Verhoeff JJ, Lavini C, van Linde ME, et al. Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma. Ann Oncol. 2010 Aug;21(8):1723-7.

32. Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009;115(8):1734-43.

33. Agha CA, Ibrahim S, Hassan A, et al. Bevacizumab is active as a single agent against recurrent malignant gliomas. Anticancer Res. 2010;30(2):609-11.

34. Chamberlain MC, Johnston S. Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol. 2009;91(3):359-67.

35. Omuro AM, Delattre JY. What is the place of bevacizumab and irinotecan in the treatment of glioblastoma and other malignant gliomas? Curr Opin Neurol. 2008;21(6):717-9.

36. Khan MK, Hunter GK, Vogelbaum M, et al. Evidence-based adjuvant therapy for gliomas: current concepts and newer developments. Indian J Cancer. 2009;46(2):96-107.

37. Gutin PH, Iwamoto FM, Beal K, et al. Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 2009;75(1):156-63.

38. Quant EC, Norden AD, Drappatz J, et al. Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. Neuro Oncol. 2009;11(5):550-5.

39. Wright KD, Gajjar A. New chemotherapy strategies and biological agents in the treatment of childhood ependymoma. Childs Nerv Syst. 2009;25(10):1275-82.

40. Chamberlain MC, Raizer J. Antiangiogenic therapy for high-grade gliomas. CNS Neurol Disord Drug Targets. 2009;8(3):184-94.

41. Chamberlain MC. Emerging clinical principles on the use of bevacizumab for the treatment of malignant gliomas. Cancer. 2010 May 28.

42. Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008;70(10):779-87.

43. Cohen MH, Shen YL, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009;14(11):1131-8.

44. Miller KD, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Eng J Med.2007;357(26):2666-2676.

45. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol.2009;27(5):740-745.

46. Hurwitz H, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med.2004;350(23):2335-2342.

47. Giantonio BJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from Eastern Cooperative Oncology Group study E2300. 2007;25(12):1539-1544.

48. Hochster HS, et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or withoug bevacizumab as first-line treatment of metastatic colorectal cancer: results of TREE study. J Clin Oncol.2008;26(28):3523.

49. Saltz LB, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol.2008;26(12):2013-2019.

50. Kabbinavar F, et al. Phase II, randomized trial compairing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol.2003;23(1):60-65.

51. Ramalingam SS, et al. Outcomes for elderly, advanced-stage non-small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group trial 4599. J Clin Oncol.2008;22(1):60-65.

52. Sandler A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Eng J Med.2006;355(24):318.

53. Johnson DH, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small cell lung cancer. J Clin Oncol.2004;22(11):2184-2191.

54. Escudier B, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet.2007;370(9605):2103-2111.

55. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Non-small cell lung cancer. v.4.2019. [NCCN Web site]. 04/29/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf. Accessed April 30, 2019.

56. Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four Arm-Cooperative study in Japan. Ann Oncol.2007;18(2):317-323.

57. National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium™.Bevacizumab (Avastin®). 2019. [NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed April 23, 2019.

58. Petrelli N, Herrera L, Rustum Y, et al. A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol. 1987;5(10):1559-65.

59. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Breast cancer. v.1.20197. [NCCN Web site]. 03/14/2019. Available at: http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed April 23, 2019.

60. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Central nervous system cancers. v.1.2019. [NCCN Web site]. 03/05/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cns_blocks.pdf. Accessed April 30, 2019.

61. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Colon cancer. v.1.2019. [NCCN Web site]. 03/15/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf . Accessed April 29, 2019.

62. Hurwitz HI, Fehrenbacher L, Hainsworth JD, et al. Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol. 2005;23(15):3502-8.

63. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Rectal cancer. v.1.2019. [NCCN Web site]. 04/25/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/rectal_blocks.pdf . Accessed April 30, 2019.

64. Emmanouilides C, Sfakiotaki G, Androulakis N, et al. Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. BMC Cancer. 2007;7:91.

65. Cheeseman SL, Joel SP, Chester JD, et al. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer. 2002;87(4):393-9.

66. Cassidy J, Clarke S, Díaz-Rubio E, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008;26(12):2006-12.

67. Fuchs CS, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25(30):4779-86.

68. André T, Louvet C, Maindrault-Goebel F, et al. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 1999;35(9):1343-7.

69. Abdalla EK, Eng C, Madary A, Vauthey JN; Southwest Oncology Group 0408. Phase II trial of neoadjuvant capecitabine/oxaliplatin/bevacizumab for resectable colorectal metastases in the liver. Clin Colorectal Cancer. 2006;5(6):436-9.

70. Cassidy J, Tabernero J, Twelves C, et al. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004;22(11):2084-91.

71. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Ovarian cancer, including fallopian tube cancer and primary peritoneal cancer. v.1.2019. [NCCN Web site]. 03/08/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ovarian_blocks.pdf . Accessed April 26, 2019.

72. Escudier B, Bellmunt J, Négrier S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol. 2010;28(13):2144-50.

73. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Kidney cancer. v.4.2019. [NCCN Web site]. 04/25/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney_blocks.pdf . Accessed April 26, 2019.

74. Tao X, Sood AK, Deavers MT, et al. Anti-angiogenesis therapy with bevacizumab for patients with ovarian granulosa cell tumors. Gynecol Oncol. 2009;114(3):431-6.

75. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Soft Tissue Sarcoma. v.2.2019. [NCCN Web site]. 02/07/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/sarcoma_blocks.pdf . Accessed April 26, 2019.

76. Park MS, Patel SR, Ludwig JA, et al. Activity of temozolomide and bevacizumab in the treatment of locally advanced, recurrent, and metastatic hemangiopericytoma and malignant solitary fibrous tumor. Cancer. 2011;117(21):4939-47.

77. Agulnik M, Yarber JL, Okuno SH, et al. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2012 Aug 21.

78. Taillibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology. 2009;72(18):1601-6.

79. Soffietti R, Rudà R, Trevisan E, et al. Phase II study of bevacizumab and nitrosourea in patients with recurrent malignant glioma: A multicenter Italian study. J Clin Oncol. 2009; 27:15s(suppl; abstr 2012).

80. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Uterine Neoplasms. v.3.2019. [NCCN Web site]. 02/27/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine_blocks.pdf . Accessed April 30, 2019.

81. Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65.

82. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50.

83. Kitagawa R, Katsumata N, Shibata T, et al. Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505. J Clin Oncol. 2015 Jul 1;33(19):2129-35.

84. Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43.

85. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1065-75.

86. US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Mvasi™(bevacizumab-awwb). Package insert. [FDA Web site]. 09/14/17. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761028 . Accessed April 26, 2019.

87. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Malignant Pleural Mesothelioma. v.2.2019. [NCCN Web site]. 04/01/2019. Available at: https://www.nccn.org/professionals/physician_gls/PDF/mpm.pdf . Accessed April 30, 2019.

88. Vaccaro V, Fabi A, Vidiri A, et al. Activity and Safety of Bevacizumab Plus Fotemustine for Recurrent Malignant Gliomas. Biomed Res Int 2014;2014:351252.

89. Wick W, Gorlia T, Bendszus M, et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med. 2017 Nov 16;377(20):1954-1963.

90. Soffietti R, Trevisan E, Bertero L, et al. Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology). J Neurooncol. 2014 Feb;116(3):533-41.

91. Lou E, Sumrall AL, Turner S,et al. Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series. J Neurooncol. 2012 Aug;109(1):63-70.

92. Nayak L, Iwamoto FM, Rudnick JD, et al. Atypical and anaplastic meningiomas treated with bevacizumab. J Neurooncol. 2012 Aug;109(1):187-93.

93. Pfisterer J, Dean AP, Baumann K, et al: Carboplatin/pegylated liposomal doxorubicin/bevacizumab (CD-BEV) vs. carboplatin/gemcitabine/bevacizumab (CG-BEV) in patients with recurrent ovarian cancer. 2018 ESMO Congress. Abstract 933O. Presented October 19, 2018.


Version Effective Date: 10/01/2019
Version Issued Date: 10/02/2019
Version Reissued Date: N/A

Connect with Us        


© 2017 Independence Blue Cross.
Independence Blue Cross is an independent licensee of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.