Sunflower Health Plan AVASTIN, Bevacizumab ZIRABEV MVASI Form

Bevacizumab (Avastin®) and its biosimilars [bevacizumab-maly (Alymsys®), bevacizumab-tnjn (Avzivi®), bevacizumab-awwb (Mvasi®), bevacizumab-adcd (Vegzelma™), bevacizumab-bvzr (Zirabev™)] are vascular endothelial growth factor-specific angiogenesis inhibitors. FDA Approved Indication(s) Avastin, Alymsys, Avzivi, Mvasi, Vegzelma, and Zirabev are indicated for the treatment of: • Metastatic colorectal cancer (CRC), in combination with intravenous 5-fluorouracil (5-FU)- based chemotherapy for first- or second-line treatment • Metastatic CRC, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine- oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen • Unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel for first-line treatment • Recurrent glioblastoma in adults • Metastatic renal cell carcinoma (RCC) in combination with interferon alfa • Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan • Epithelial ovarian, fallopian tube, or primary peritoneal cancer: o In combination with carboplatin and paclitaxel, followed by Avastin/Mvasi/Vegzelma Zirabev as a single agent, for stage III or IV disease following initial surgical resection o In combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent disease who received no more than 2 prior chemotherapy regimens o In combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by Avastin/Mvasi/Vegzelma/Zirabev as a single agent, for platinum-sensitive recurrent disease Avastin is also indicated for the treatment of: • Hepatocellular carcinoma (HCC) in combination with atezolizumab for patients with unresectable or metastatic HCC who have not yet received prior systemic therapy. Limitation(s) of use: Bevacizumab products are not indicated for adjuvant treatment of colon cancer. Page 1 of 19 CLINICAL POLICY Bevacizumab and Biosimilars Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Avastin, Alymsys, Avzivi, Mvasi, Vegzelma, and Zirabev are medically necessary when the following criteria are met: I. Initial Approval Criteria A. FDA-Approved Indications (must meet all): 1. Diagnosis of one of the following (a-g): a. CRC; b. Non-squamous NSCLC; c. Glioblastoma; d. Metastatic RCC; e. Cervical cancer; f. Epithelial ovarian, fallopian tube, or primary peritoneal cancer; g. HCC; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Member meets one of the following (a-g): a. For CRC, disease is advanced, metastatic, or unresectable and bevacizumab is used in combination with one of the following (i-vi): i. 5-FU/leucovorin or capecitabine-based chemotherapy; ii. IROX (irinotecan and oxaliplatin); iii. FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin); iv. Irinotecan or FOLFIRI (fluorouracil, leucovorin, and irinotecan); v. FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin); vi. Lonsurf® if previously progressed through all available regimens; b. For recurrent, advanced, or metastatic non-squamous NSCLC, prescribed as one of the following (i-v): i. Single agent therapy; ii. In combination with carboplatin and paclitaxel for first line treatment; iii. In combination with pemetrexed; iv. In combination with Tecentriq®; v. In combination with erlotinib for sensitizing EGFR mutation-positive histology; c. For glioblastoma, member has recurrent disease or requires symptom management; d. For metastatic RCC, used as a single-agent or in combination with everolimus or erlotinib (for advanced papillary RCC including hereditary leiomyomatosis and renal cell cancer); e. For persistent, recurrent, or metastatic cervical cancer, used in one of the following ways (i, ii or iii): i. As a single agent; Page 2 of 19 CLINICAL POLICY Bevacizumab and Biosimilars ii. In combination with paclitaxel and cisplatin, carboplatin, or topotecan; iii. In combination with Keytruda®, paclitaxel, and cisplatin/carboplatin for PD- L1-postive disease; f. For epithelial ovarian, fallopian tube, or primary peritoneal cancer, one of the following (i-vi): i. Prescribed in combination with a platinum agent (e.g., carboplatin, oxaliplatin) and chemotherapy, followed by bevacizumab as a single agent, for Stage IB-IV disease; ii. Prescribed for maintenance in combination with Lynparza® for stage II-IV disease; iii. Prescribed in combination with Zejula® as targeted therapy for platinum- sensitive persistent disease or recurrence; iv. For platinum-resistant disease, prescribed in combination with paclitaxel, pegylated liposomal doxorubicin, topotecan, gemcitabine, or cyclophosphamide; v. For platinum-sensitive disease, prescribed in combination with carboplatin and paclitaxel, or carboplatin and gemcitabine, or carboplatin and liposomal doxorubicin, followed by bevacizumab as a single agent; vi. Prescribed as a single agent; g. For unresectable or metastatic HCC, used in combination with Tecentriq as first- line systemic therapy, and: i. HCC is classified as Child-Pugh class A or B; 5. For Alymsys, Avastin, Avzivi, or Vegzelma requests, member meets one of the following (a or b): a. Member must use Mvasi or Zirabev, unless both are contraindicated or clinically significant adverse effects are experienced;* *Prior authorization may be required for Mvasi and Zirabev b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); 6. Request meets one of the following (a or b):* a. Dose does not exceed 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks (see Appendix F for dose rounding guidelines); b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less B. Oncology - Non-FDA-Approved Adult Indications (off-label) (must meet all): 1. Diagnosis of one of the following conditions (a-m): a. Adult glioma of one of the following types (i, ii, or iii): i. Oligodendroglioma that is IDH-mutant, 1p19q codeleted; ii. IDH-mutant astrocytoma; iii. Circumscribed glioma; b. Ampullary adenocarcinoma – intestinal type; c. Endometrial carcinoma; Page 3 of 19 CLINICAL POLICY Bevacizumab and Biosimilars d. Intracranial and spinal ependymoma; e. Peritoneal mesothelioma; f. Pleural mesothelioma; g. Medulloblastoma; h. Meningioma; i. Metastatic spine tumors or brain metastases; j. Primary central nervous system lymphoma; k. Small bowel adenocarcinoma; l. Soft tissue sarcoma – solitary fibrous tumor or angiosarcoma; m. Vulvar cancer – adenocarcinoma or squamous cell carcinoma; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. For Alymsys, Avastin, Avzivi, or Vegzelma requests, member meets one of the following (a or b): a. Member must use Mvasi or Zirabev, unless both are contraindicated or clinically significant adverse effects are experienced;* *Prior authorization may be required for Mvasi and Zirabev b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); 5. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).* *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less C. Oncology - Non-FDA-Approved Pediatric Indications (off-label) (must meet all): 1. Diagnosis of difuse high-grade glioma; 2. Prescribed by or in consultation with an oncologist; 3. Age < 18 years; 4. For Alymsys, Avastin, Avzivi, or Vegzelma requests, member meets one of the following (a or b): a. Member must use Mvasi or Zirabev, unless both are contraindicated or clinically significant adverse effects are experienced;* *Prior authorization may be required for Mvasi and Zirabev b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); 5. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).* *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less Page 4 of 19 CLINICAL POLICY Bevacizumab and Biosimilars D. Ophthalmology - Non-FDA-Approved Indications (off-label) (must meet all): 1. Diagnosis of one of the following conditions (a-g): a. Neovascular (wet) age-related macular degeneration; b. Macular edema following retinal vein occlusion; c. Diabetic macular edema; d. Proliferative diabetic retinopathy; e. Neovascular glaucoma; f. Choroidal neovascularization associated with: angioid streaks, no known cause, inflammatory conditions, high pathologic myopia, or ocular histoplasmosis syndrome; g. Diabetic retinopathy associated with ocular neovascularization (choroidal, retinal, iris); 2. Age ≥ 18 years; 3. Request is for bevacizumab intravitreal solution; *Requests for IV formulations of Avastin, Alymsys, Avzivi, Mvasi, Vegzelma, and Zirabev will not be approved 4. Request meets one of the following (a or b): a. Dose does not exceed 2.5 mg per dose; b. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off- label use (prescriber must submit supporting evidence). Approval duration: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less E. Other diagnoses/indications (must meet all): 1. For Alymsys, Avastin, Avzivi, or Vegzelma requests for non-ophthalmology uses, member meets one of the following (a or b): a. Member must use Mvasi or Zirabev, unless both are contraindicated or clinically significant adverse effects are experienced;* *Prior authorization may be required for Mvasi and Zirabev b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); 2. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or 3. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 2 above does not apply, refer to the off-label use policy for the relevant line Page 5 of 19 CLINICAL POLICY Bevacizumab and Biosimilars of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. II. Continued Therapy A. All Indications in Section I (must meet all): 1. Member meets one of the following (a, b, or c): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B); c. Documentation supports that member is currently receiving Alymsys, Avastin, Avzivi, Mvasi, Vegzelma, or Zirabev for a covered oncology indication listed in section I and has received this medication for at least 30 days; 2. Member is responding positively to therapy; 3. For Alymsys, Avastin, Avzivi, or Vegzelma requests for non-ophthalmology uses, member meets one of the following (a or b): a. Member must use Mvasi or Zirabev, unless both are contraindicated or clinically adverse effects are experienced;* *Prior authorization may be required for Mvasi and Zirabev b. Request is for treatment associated with cancer for a State with regulations against step therapy in advanced oncology settings (see Appendix E); 4. If request is for a dose increase, request meets one of the following (a or b):* a. New dose does not exceed 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks (see Appendix F for dose rounding guidelines); b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed chemotherapy regimen must be FDA-approved or recommended by NCCN Approval duration: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 and either 2 or 3): 1. For Alymsys, Avastin, Avzivi, or Vegzelma requests for non-ophthalmology uses, member meets one of the following (a or b): a. Member must use Mvasi or Zirabev, unless both are contraindicated or clinically significant adverse effects are experienced;* *Prior authorization may be required for Mvasi and Zirabev b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E); 2. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or Page 6 of 19 CLINICAL POLICY Bevacizumab and Biosimilars b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or 3. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 2 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key 5-FU: fluorouracil CapeOX: capecitabine, oxaliplatin CRC: colorectal cancer FDA: Food and Drug Administration FOLFIRI: fluorouracil, leucovorin, irinotecan FOLFIRINOX: fluorouracil, leucovorin, irinotecan, oxaliplatin FOLFOX: fluorouracil, leucovorin, oxaliplatin HCC: hepatocellular carcinoma IDH: isocitrate dehydrogenase gene IROX: irinotecan, oxaliplatin NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer PD-L1: programmed death-ligand 1 RCC: renal cell carcinoma Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose Metastatic carcinoma of the colon or rectum FOLFOX4 = Infusional 5- FU/leucovorin/ oxaliplatin Varies Oxaliplatin 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 600 mg/m2 IV 5-FU continuous infusion over 22 hours on days 1 & 2. Repeat cycle every 14 days. Camptosar 180 mg/m2 IV over 90 Varies Page 7 of 19 FOLFIRI = Infusional 5-FU/ CLINICAL POLICY Bevacizumab and Biosimilars Drug Name Dosing Regimen leucovorin/Camptosar (irinotecan) minutes day 1; Leucovorin 400 Dose Limit/ Maximum Dose capecitabine (Xeloda) IROX = oxaliplatin/Camptosar (irinotecan) Camptosar (irinotecan) 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 46 hours. Repeat cycle every 14 days. 2500 mg/m2 PO BID for 2 weeks; repeat cycles of 2 weeks on and 1 week off. For patients who cannot tolerate intensive therapy. Oxaliplatin 85 mg/m2 IV followed by Camptosar 200 mg m2 IV over 30-90 minutes every 3 weeks 180 mg/m2 IV every 2 weeks or 300-350 mg/m2 IV every 3 weeks Varies Varies Varies Trifluridine 80 mg/dose Lonsurf® (trifluridine and tipiracil) 35 mg/m2 (based on trifluridine component) PO BID on days 1-5 and 8-12, repeated every 28 days NSCLC Examples of drugs used in single- or multi-drug chemotherapy regimens: • Cisplatin, carboplatin, paclitaxel, Various doses Varies docetaxel, vinorelbine, gemcitabine, etoposide, irinotecan, vinblastine, mitomycin, ifosfamide, pemetrexed disodium, (Alimta®) erlotinib (Tarceva®), Tecentriq® (atezolizumab) Ovarian Cancer Examples of drugs used in single- or multi-drug chemotherapy regimens: • carboplatin and paclitaxel, docetaxel and carboplatin, Lynparza® (olaparib), Glioblastoma Multiforme temozolomide (Temodar) carmustine (Bicnu) Various doses Varies Maintenance phase cycles: 150 mg- 200 mg/m² PO days 1-5. Repeat every 28 days. 150 mg to 200 mg/m² IV on day Varies Varies Page 8 of 19 CLINICAL POLICY Bevacizumab and Biosimilars Drug Name Dosing Regimen Dose Limit/ Maximum Dose 1. Repeat every 6-8 weeks for one year or tumor progression. Various doses Varies Cervical Cancer Examples of drugs used in multi- drug chemotherapy regimens: • cisplatin/paclitaxel, carboplatin/paclitaxel, cisplatin/topotecan (Hycamtin), topotecan/paclitaxel Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Fatal pulmonary hemorrhage can occur in patients with NSCLC treated with chemotherapy and bevacizumab. 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 bevacizumab. Appendix E: States with Regulations against Redirections in Certain Oncology Settings State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH OK PA TN TX Yes Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat the cancer or any symptom thereof of the covered person *Applies to Commercial and HIM requests only* For stage 4 metastatic cancer and associated conditions *Applies to HIM requests only* For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions Page 9 of 19 CLINICAL POLICY Bevacizumab and Biosimilars Appendix F: Dose Rounding Guidelines Weight-based Dose Range ≤ 104.99 mg 105 mg-209.99 mg 210 mg-314.99 mg 315 mg-419.99 mg 420 mg-524.99 mg 525 mg-629.99 mg 630 mg-734.99 mg 735 mg-839.99 mg 840 mg-944.99 mg 945 mg-1,049.99 mg 1,050 mg-1,154.99 mg 1,155 mg-1,259.99 mg 1,260 mg-1,364.99 mg 1,365 mg-1,469.99 mg 1,470 mg-1,574.99 mg 1,575 mg-1,679.99 mg 1,680 mg-1,784.99 mg 1,785 mg-1,889.99 mg 1,890 mg-1,994.99 mg 1,995 mg-2,099.99 mg Vial Quantity Recommendation 1 vial of 100 mg/4 mL 2 vials of 100 mg/4 mL 3 vials of 100 mg/4 mL 1 vial of 400 mg/16 mL 1 vial of 100 mg/4 mL and 1 vial of 400 mg/16 mL 2 vials of 100 mg/4 mL and 1 vial of 400 mg/16 mL 3 vials of 100 mg/4 mL and 1 vial of 400 mg/16 mL 2 vials of 400 mg/16 mL 1 vials of 100 mg/4 mL and 2 vials of 400 mg/16 mL 2 vials of 100 mg/4 mL and 2 vials of 400 mg/16 mL 3 vials of 100 mg/4 mL and 2 vials of 400 mg/16 mL 3 vials of 400 mg/16 mL 1 vials of 100 mg/4 mL and 3 vials of 400 mg/16 mL 2 vials of 100 mg/4 mL and 3 vials of 400 mg/16 mL 3 vials of 100 mg/4 mL and 3 vials of 400 mg/16 mL 4 vials of 400 mg/16 mL 1 vials of 100 mg/4 mL and 4 vials of 400 mg/16 mL 2 vials of 100 mg/4 mL and 4 vials of 400 mg/16 mL 3 vials of 100 mg/4 mL and 4 vials of 400 mg/16 mL 5 vials of 400 mg/16 mL V. Dosage and Administration Indication Metastatic CRC Maximum Dose 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks Dosing Regimen 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 NSCLC 15 mg/kg IV infusion every 3 weeks with carboplatin/paclitaxel 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks Page 10 of 19 CLINICAL POLICY Bevacizumab and Biosimilars Indication Ovarian cancer, stage III or IV disease following initial surgical resection Dosing Regimen 15 mg/kg IV infusion every 3 weeks with carboplatin/paclitaxel for up to 6 cycles, followed by bevacizumab 15 mg/kg every 3 weeks as a single agent Platinum resistant ovarian cancer 10 mg/kg intravenously every 2 weeks with weekly paclitaxel, liposomal doxorubicin, or topotecan Platinum sensitive ovarian cancer 15 mg/kg intravenously every 3 weeks with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by bevacizumab 15 mg/kg every 3 weeks as a single agent Maximum Dose 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks 15 mg/kg IV every 3 weeks HCC 15 mg/kg IV every 3 weeks plus Tecentriq 1,200 mg IV on the same day 15 mg/kg IV every 3 weeks Clear cell renal carcinoma 10 mg/kg IV every 2 weeks with interferon alfa Glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma 10 mg/kg IV every 2 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 Neovascular (wet) macular degeneration 1.25 to 2.5 mg administered by intravitreal injection every 4 weeks 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks 2.5 mg/dose Page 11 of 19 CLINICAL POLICY Bevacizumab and Biosimilars Indication Neovascular glaucoma Dosing Regimen 1.25 mg administered by intravitreal injection every 4 weeks Maximum Dose 2.5 mg/dose Macular edema secondary to retinal vein occlusion 1 mg to 2.5 mg administered by intravitreal injection every 4 weeks 2.5 mg/dose Proliferative diabetic retinopathy 1.25 mg administer by intravitreal injection 5 to 20 days before vitrectomy 2.5 mg/dose Diabetic macular edema 1.25 mg administered by intravitreal injection 2.5 mg/dose Malignant mesothelioma of pleura Metastatic CRC in previously untreated elderly patients ineligible for oxaliplatin- or irinotecan- based chemotherapy 15 mg/kg IV (plus pemetrexed 500 mg/m(2) IV and cisplatin 75 mg/m(2) IV) every 21 days for up to 6 cycles, followed by maintenance bevacizumab 15 mg/kg every 21 days until disease progression or unacceptable toxicity. All patients should receive folic acid 400 mcg orally daily and vitamin B12 1000 mcg IM every 3 weeks, both beginning 7 days prior to pemetrexed and continuing for 3 weeks following the last pemetrexed dose (off-label dosage). 7.5 mg/kg IV on day 1 with capecitabine 1,000 mg/m2 orally twice daily on days 1 to 14, given every 3 weeks until disease progression. 2.5 mg/dose 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks. VI. Product Availability Single-use vials: 100 mg/4 mL, 400 mg/16 mL VII.