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Prior Authorization Protocol

AVASTINR (bevacizumab)

NATL

Coverage of drugs is first determined by the memberís pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • Metastatic colorectal cancer, with intravenous 5-fluorouracil-based (5-FU) chemotherapy for first- or second-line treatment.
    • Metastatic colorectal cancer, with fluoropyrimidine- irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line Avastin- containing regimen
    • Non-squamous, non-small cell lung cancer, with carboplatin and paclitaxel for the first line treatment of unresectable, locally advanced, recurrent or metastatic disease.
    • Glioblastoma, as a single agent for adult patients with progressive disease following prior therapy.
      • Effectiveness based on improvement in objective response rate. No data available demonstrating improvement in disease-related symptoms or survival with Avastin.
    • Metastatic renal cell carcinoma with interferon alpha
    • Cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease.
    • For treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with paclitaxel, pegylated liposomal doxorubin or topotecan.
  2. Health Net Approved Indications and Usage Guidelines:
    Approve for any of the following:
    • Diagnosis of Neovascular (Wet) Age-Related Macular Degeneration confirmed by an ophthalmologist
    • Diagnosis of Neovascular Glaucoma and failure of maximal doses of one approved antiglaucoma medication.
    • Diagnosis of proliferative diabetic retinopathy and patient will be undergoing vitrectomy
    • Diagnosis of macular edema secondary to retinal vein occlusion
    • Diagnosis of diabetic macular edema
    • Diagnosis of metastatic carcinoma of the colon or rectum and used in combination with a 5-fluorouracil-based chemotherapy regimen
    • Diagnosis of metastatic carcinoma of the colon or rectum in patients whose disease has progressed following an Avastin containing regimen and used in combination with fluoropyrimidine- irinotecan- or fluoropyrimidine-oxaliplatin chemotherapy regimen
    • Diagnosis of non-squamous, non-small cell lung carcinoma (NSCLC) and used in combination with platinum-based systemic chemotherapy (e.g. cisplatin, carboplatin) and paclitaxel
    • Diagnosis of ovarian cancer and failure or clinically significant adverse effects to two chemotherapy regimens
    • Diagnosis of relapsed or medically unresectable stage IV renal carcinoma and used in combination with interferon alfa-2a
    • Recurrence or salvage therapy of Glioblastoma Multiforme, Anaplastic Astrocytoma or Anaplastic Oligoendroglioma as a single agent or in combination with irinotecan, carmustine, lomustine, temozolomide, or carboplatin
    • Diagnosis of soft tissue sarcoma
    AND
      • Angiosarcoma
    OR
      • Solitary fibrous tumor/hemangiopericytoma
    • Diagnosis of persistent, recurrent, or metastatic cervical cancer and used in combination with paclitaxel and cisplatin or paclitaxel and topotecan
    • Diagnosis of platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with paclitaxel, pegylated liposomal doxorubin or topotecan.
  3. Coverage is Not Authorized For:
    • Metastatic carcinoma of the colon or rectum: use as a single agent. Avastin as a single agent resulted in inferior survival rates when compared to FOLFOX regimen.
    • NSCLC: patients with squamous histology due to increased risk of hemoptysis.
    • The addition of Avastin to gemcitabine as first line therapy for carcinoma of the pancreas did not improve survival in advanced pancreatic cancer in comparison to gemcitabine given alone.
    • Avastin monotherapy for use in hormone refractory prostate cancer was shown to be relatively ineffective in a small study of fifteen patients. The McGill Present Pain Index indicated a trend toward increasing pain during the study.
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section unless there is sufficient documentation of efficacy and safety in the published literature.
  4. General Information:
    • The FDA revoked the approval of the breast cancer indication for Avastin (bevacizumab) on November 18, 2011. Avastin used for metastatic breast cancer has not been shown to provide a benefit, in terms of delay in the growth of tumors, that would justify its serious and potentially life-threatening risks. Nor is there evidence that use of Avastin will either help women with breast cancer live longer or improve their quality of life. More information at: http://www.fda.gov/NewsEvents/Newsroom/ucm279485.htm
    • Fatal pulmonary hemorrhage can occur in patients with NSCLC treated with chemotherapy and Avastin. The incidence of severe or fatal hemoptysis was 31% in patients with squamous histology and 2.3% with NSCLC excluding predominant squamous histology. Patients with recent hemoptysis should not receive Avastin.
    • Avastin has been added to the NCCN practice guidelines as category 2A for recurrent ovarian cancer for patients who have progressed on two consecutive single-agent regimens without evidence of clinical benefit.
    • Age-related macular degeneration, secondary to choroidal neovascularization
      • In a prospective time-series trial, bevacizumab 2.5 mg was administered by intravitreal injection every 4 weeks for a total of 3 injections
      • In one retrospective study, bevacizumab 1.25 mg was administered by intravitreal injection once monthly for a total of three injections.
      • In another retrospective study intravitreal bevacizumab 1.25 mg was administered once monthly until macular edema, subretinal fluid and/or pigment epithelial detachment resolved (Avery et al, 2006).
    • Avastin, with or without irinotecan, has been added to the NCCN practice guidelines for recurrent or salvage therapy of Glioblastoma Multiforme and Anaplastic Astrocytoma.
    • Avastin is effective for the treatment of neovascular glaucoma that is not responsive to maximal doses of antiglaucoma medications. While most studies did not indicate the agents that were tried and failed prior to the use of Avastin in neovascular glaucoma, one study did indicate the use of timolol, dorzolamide and brimonidine before an Avastin injection.
    • Avastin is category 2A for the treatment of soft tissue sarcoma-angiosarcoma and soft tissue sarcoma-solitary fibrous tumor/hemangiopericytoma in the NCCN practice guidelines for soft tissue sarcomas.
    • Avastin is a category 2A for the treatment of adult intracranial and spinal ependymoma (excluding subependymoma).
    • Avastin is category 2A also for the treatment of non-clear cell renal carcinoma.
    • Avastin is category 2A for the treatment of endometrial carcinoma
    • Avastin in combination with cisplatin/paclitaxel has been added to the NCCN practice guidelines as category 1 for recurrent or metastatic cervical cancer. Avastin in combination with topotecan/paclitaxel has been added as a category 2B recommendation for this same indication.
    • Avastin has a black box warning for gastrointestinal perforation, surgery and wound healing complications, and hemorrhage. Avastin should be discontinued in patients with wound dehiscence. Discontinue at least 28 days prior to elective surgery. Do not initiate Avastin for at least 28 days after surgery and until the surgery wound is fully healed. Avastin causes severe or fatal hemorrhage, hemoptysis, gastrointestinal bleeding, CNS hemorrhage, and vaginal bleeding. Do not administer to patients with serious hemorrhage or recent hemoptysis.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose
    FOLFOX 4 =
    Infusional 5-FU/leucovorin/EloxatinTM (oxaliplatin)

    Metastatic carcinoma of the colon or rectum:
    Eloxatin 85 mg/m2 IV over 2 hours day 1;
    leucovorin 200 mg/m2 IV over 2 hours days 1 & 2,
    followed by 5-FU 400 mg/m2 IV bolus over 2-4 minutes,
    followed by 600m g/m2 IV 5-FU continuous infusion over 22 hours
    on days 1 & 2.
    Repeat cycle every 14 days.

    Not Listed

    FOLFIRI =
    Infusional 5-FU/leucovorin/CamptosarR (irinotecan)

    Metastatic carcinoma of the colon or rectum:
    Camptosar 180 mg/m2 IV over 90 minutes day 1;
    Leucovorin 400 mg/m2 IV over 2 hours day 1 followed by
    5-FU 400 mg/m2 IV bolus over 2-4 minutes,
    followed by 2.4 gm/m2 IV 5-FU continuous infusion over 4-6 hours.
    Repeat cycle every 14 days.

    Not Listed

    Xeloda R
    (capecitabine)

    Metastatic carcinoma of the colon or rectum:
    2500 mg/m2 PO daily divided Q12h for 2 weeks;
    repeat cycles of 2 weeks on and 1 week off.
    For patients who cannot tolerate intensive therapy.

    Not Listed

    Cisplatin
    Carboplatin
    Paclitaxel
    Docetaxel
    Vinorelbine
    Gemcitabine
    Etoposide
    Irinotecan
    Vinblastine
    Mitomycin
    Ifosfamide
    Alimta (2nd line)

    NSCLC:
    Various doses

    Number of cycles varies

    ParaplatinTM (carboplatin )
    and
    TaxolR (paclitaxel)

    Ovarian Cancer:
    Carboplatin dosed at an area under the curve (AUC) of 5-7.5 and
    paclitaxel 175 mg/m2 IV over 3 hours given every
    3 weeks for 6 courses.

    Not listed

    TaxotereR (docetaxel)
    and
    Paraplatin (carboplatin)

    Ovarian Cancer:
    Docetaxel, 60-75 mg/m2 IV over 1 hour plus
    carboplatin dosed at AUC of 5 to 6 every 3 weeks.

    Not listed

    TemodarR
    (temozolomide)

    Glioblastoma Multiforme:
    150 mg - 200 mg/m2 PO days 1-5.
    Repeat every 28 days.

    Not Listed

    BCNUR
    (carmustine)

    Glioblastoma Multiforme:
    150 mg - 200 mg/m2 IV day 1.
    Repeat every 6-8 weeks for one year or
    tumor progression.

    Not Listed

    cisplatin/paclitaxel

    Cervical Cancer:
    Paclitaxel: I.V.: 135 mg/m2 continuous infusion over 24 hours day 1
    Cisplatin: I.V.: 50 mg/m2 day 2 Repeat cycle every 21 days for up to a total of 6 cycles; responders may continue beyond 6 cycles

    Not Listed

    cisplatin/topotecan

    Cervical Cancer:
    Topotecan: I.V.: 0.75 mg/m2/day days 1, 2, and 3
    Cisplatin: I.V.: 50 mg/m2 day 1 only Repeat cycle every 21 days for up to a total of 6 cycles; responders may continue beyond 6 cycles

    Not Listed

    topotecan/paclitaxel

    Cervical Cancer:
    Paclitaxel: I.V.: 135 mg/m2 continuous infusion over 24 hours day 1
    Topotecan: I.V.: 0.75 mg/m2/day days 1, 2, and 3 Repeat cycle every 21 days for up to a total of 6 cycles; responders may continue beyond 6 cycles

    Not Listed

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    Avastin

    Colorectal Cancer
    5 mg/kg or 10 mg/kg once every 14 days as an IV infusion in combination with a 5-FU based chemotherapy regimen until disease progression is detected
    5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks when used in combination with a fluoropyrimidine-irinotecan or
    fluoropyrimidine-oxaliplatin based chemotherapy regimen in patients who have progressed on a first-line Avastin-containing regimen

    Non-Squamous, Non-Small Cell Lung Cancer
    15 mg/kg IV infusion every 3 weeks

    Ovarian Cancer
    15 mg/kg IV infusion every 3 weeks

    Platinum Resistant Ovarian Cancer
    10 mg/kg intravenously every 2 weeks with weekly paclitaxel, liposomal doxorubicin,
    or topotecan or 15mg/kg every 3 weeks if given with topotecan every 3 weeks.


    Clear cell renal carcinoma
    10 mg/kg IV every 2 weeks

    Glioblastoma Multiforme, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma
    10 mg/kg IV every 2 weeks

    Macular edema secondary to retinal vein occlusion
    1 mg to 2.5 mg administered by intravitreal injection every 4 weeks

    Soft tissue sarcoma
    15 mg/kg IV infusion every 3 weeks

    Cervical Cancer
    15 mg/kg IV infusion every 3 weeks (in combination with paclitaxel and either cisplatin or topotecan) until disease progression or unacceptable toxicity

    Up to 1 year

    Avastin

    Neovascular (Wet) Macular Degeneration:
    1.25 to 2.5 mg administered by intravitreal injection
    every 4 weeks

    Up to 6 months

    Avastin

    Neovascular Glaucoma
    1.25 mg administered by intravitreal injection every 4 weeks

    Up to 3 months

    Avastin

    Proliferative diabetic retinopathy
    1.25 mg administer by intravitreal injection 5 to 20 days before vitrectomy

    Up to 1 month

    Avastin

    Diabetic Macular Edema
    1.25 mg administered by intravitreal injection

    Up to 5 injections

  7. Product Availability:
    Single use vials: 100 mg/4 ml, 400 mg/16 ml
  8. References:
    1. Avastin. (Prescribing information). South San Francisco, CA: Genentech, Inc. November 2014.
    2. Guide to Selected Cancer Chemotherapy Regimens and Associated Adverse Events. Amgen Oncology 4th Edition.
    3. Wright JD, Rader JS, Viviano D, et al. Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma. Cancer. 2006;107 (1) :83-89.
    4. Weigert G, Michels S, Sacu S, et al. Intravitreal bevacizumab (Avastin) therapy versus photodynamic therapy plus intravitreal triamcinolone for neovascular age-related macular degeneration: 6-month results of a prospective, randomised, controlled clinical study. Br J Ophthalmol. 2008;92:356-360.
    5. Bashshur ZF, Haddad ZA, Schakal A, et al. Intravitreal Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration: A One-year Prospective Study. Am J Ophthalmol. 2008;145: 249-256.
    6. Ladewig MS, Karl SE, Hamelmann V, et al. Combined intravitreal bevacizumab and photodynamic therapy for neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2008;246:17-25.
    7. Micromedex Web site. Available at: http://thomsonhc.com/. Accessed September 12, 2014.
    8. National Comprehensive Cancer Network. Kidney Cancer 2.2012. http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf. Accessed July 14, 2014.
    9. National Comprehensive Cancer Network. Central Nervous System Cancers. V1.2012. http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf. Accessed July 14, 2014..
    10. Yazdani S, Hendi K, Pakravan M, et al. Intravitreal bevacizumab for neovascular glaucoma: a randomized controlled trial. J Glaucoma. October-November 2009;18(8):632-637.
    11. Brouzas D, Charakidas A, Moschos M, et al. Bevacizumab (Avastin.) for the management of anterior chamber neovascularization and neovascular glaucoma. Clinical Ophthalmology. 2009;3:685-688.
    12. Moraczewski AL, Lee RK, Palmberg PF, et al. Outcomes of treatment of neovascular glaucoma with intravitreal bevacizumab. Br J Ophthalmol, 2009;93:589-593.
    13. Costagliola C, Cipollone U, Rinaldi M, et al. Inravitreal bevacizumab (Avastin.) injection for neovascular glaucoma: a survey of 23 cases throughout 12-month follow-up. Br J Clin Pharmacol, 2008;66(5):667-673.
    14. di Lauro R, De Ruggiero P, di Lauro R, di Lauro MT, Romano MR. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2010;248:785-791.
    15. Rizzo S, Genovesi-Ebert F, Di Bartolo E, Vento A, Miniaci S, Williams G. Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Graefes Arch Clin Exp Ophthalmol. 2008 Jun;246(6):837-842.
    16. Arevalo JF, Sanchez JG, Wu L, et al. Primary intravitreal bevacizumab for diffuse diabetic macular edema. Ophthalmology. August 2009;116(8):1488-1497.
    17. Roh MI, Byeon SH, Kwon OW. Repeated intravitreal injection of bevacizumab for clinically significant diabetic macular edema. Retina, the Journal of Retinal and Vitreous Diseases. 2008; 28(9): 1314-1318.
    18. Kook D, Wolf A, Kreutzer T, et al. Long-term effect of intravitreal bevacizumab (Avastin) in patients with chronic diffuse diabetic macular edema. Retina, the Journal of Retinal and Vitreous Diseases. 2008; 28(8): 1053-1060.
    19. National Comprehensive Cancer Network. Soft Tissue Sarcomas. V2.2012. http://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Accessed July 14, 2014.
    20. Clinical Pharmacology Web site. Available at: http://cpip.gsm.com/. Accessed July 14, 2014.
    21. Avastin. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed July 14, 2014.
    22. National Comprehensive Cancer Network. Cervical Cancer. V1.2015. http://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed September 12, 2014.
    23. Lexi-Comp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; Accessed September 12, 2014.
    24. Tewari KS, Sill MW, Long HJ, et al. Improved survival with bevacizumab in advanced cervical cancer. New England Journal of Medicine. 2014; 370(8): 734-743.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.