TECENTRIQ, Atezolizumab Form

Atezolizumab (Tecentriq®) is a programmed death-ligand 1 (PD-L1) blocking antibody. FDA Approved Indication(s) Tecentriq is indicated: • Non-small cell lung cancer (NSCLC) o As adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test. o For the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the tumor area [IC ≥ 10%] ), as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. o In combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations.
o In combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. o For the treatment of adult patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving Tecentriq. • Small cell lung cancer (SCLC) o In combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). • Heptatocellular carcinoma (HCC) o In combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy.
• Melanoma o In combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. • Alveolar soft part sarcoma (ASPS) o For the treatment of adult and pediatric patients 2 years of age and older with unresectable or metastatic ASPS.
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CLINICAL POLICY Atezolizumab 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 Tecentriq is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Non-Small Cell Lung Cancer (must meet all):

1. Diagnosis of NSCLC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a, b, or c): a. For stage II to III NSCLC, prescribed as a single agent and meets one of the following (i or ii):
      i. Member has had previous resection;
      ii. Member has all the following (1, 2 and 3): 1) High-risk stage IIA or stage IIIB NSCLC (see Appendix D); 2) PD-L1 expression ≥ 1%;
      3) Previously received platinum-containing chemotherapy (see Appendix B); b. For member with both a negative or unknown EGFR or ALK mutation status AND recurrent, advanced, or metastatic NSCLC: Member meets one of the following (i, ii, iii, or iv): i. Request is for use as a single agent as first-line therapy for tumors that have high PD-L1 expression (PD-L1 ≥ 50% [TC ≥ 50%] or tumor-infiltrating IC covering ≥ 10% of the tumor area [IC ≥ 10%]); ii. Disease is non-squamous, and Tecentriq is prescribed in combination with one of the following (1 or 2): 1) Bevacizumab, paclitaxel, and carboplatin; 2) Paclitaxel protein-bound (Abraxane®) and carboplatin; iii. Member has previously received platinum-containing chemotherapy (see Appendix B); iv. If no prior progression on a PD-1/PD-L1 inhibitor (i.e., Tecentriq as well as nivolumab, pembrolizumab, durvalumab), request is for single agent as subsequent therapy; c. For member with a positive EGFR or ALK mutation status AND recurrent, advanced, or metastatic NSCLC: Member has a history of disease progression during or following an NCCN-recommended therapy for the specific mutation (see Appendix B);

2. Request meets one of the following (a or b): a. Dose does not exceed 1,680 mg every 4 weeks;
   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 Page 2 of 12

   CLINICAL POLICY Atezolizumab Commercial – 6 months or duration of request, whichever is less B. Small Cell Lung Cancer (must meet all):

   1. Diagnosis of extensive-stage SCLC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with carboplatin and etoposide;
   5. Request meets one of the following (a or b): a. Dose does not exceed 1,680 mg every 4 weeks;
      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 – 6 months or duration of request, whichever is less C. Hepatocellular Carcinoma (must meet all):

3. Diagnosis of HCC;

   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with bevacizumab as first-line systemic therapy;
   5. Confirmation of Child-Pugh class A or B status;
   6. Request meets one of the following (a or b): a. Dose does not exceed 1,680 mg every 4 weeks;
      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 – 6 months or duration of request, whichever is less D. Melanoma (must meet all):
   7. Diagnosis of melanoma;
   8. Prescribed by or in consultation with an oncologist;
   9. Age ≥ 18 years;
   10. Prescribed in combination with cobimetinib and vemurafenib;
   11. One of the following (a or b):
       a. For member with BRAF V600 mutation AND unresectable or metastatic melanoma;
       b. Request is for use as re-induction therapy;
   12. Request meets one of the following (a or b): a. Dose does not exceed 1,680 mg every 4 weeks;
       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 Page 3 of 12

   CLINICAL POLICY Atezolizumab Commercial – 6 months or duration of request, whichever is less E. Alveolar Soft Part Sarcoma (must meet all):

4. Diagnosis of ASPS;
   2. Disease is unresectable or metastatic;
   3. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 2 years;
   5. Prescribed as a single-agent therapy;
   6. Request meets one of the following (a or b): a. Dose does not exceed one of the following (i or ii):
      i. Adults: 1,680 mg every 4 weeks;
      ii. Pediatrics: 15 mg/kg (up to a maximum of 1,200 mg) every 3 weeks;
      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 – 6 months or duration of request, whichever is less F. Peritoneal Mesothelioma (off-label) (must meet all):
5. Diagnosis of peritoneal mesothelioma;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with bevacizumab as subsequent systemic therapy;
   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 – 6 months or duration of request, whichever is less G. Urothelial Carcinoma (off-label) (must meet all):
6. Diagnosis of urothelial carcinoma (UC);
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. One of the following (a or b): a. Member is ineligible for cisplatin-containing chemotherapy, and the tumor expresses PD-L1; b. Member is ineligible for any platinum-containing chemotherapy (e.g., cisplatin, carboplatin, oxaliplatin) regardless of PD-L1 status;

7. Prescribed as a single agent;

   6. 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:
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   CLINICAL POLICY Atezolizumab Medicaid/HIM – 6 months Commercial – 6 months or duration of request, whichever is less H. Cervical Cancer (off-label) (must meet all)

8. Diagnosis of small cell neuroendocrine carcinoma of the cervix;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is persistent, recurrent or metastatic;
   5. Prescribed in combination with cisplatin/carboplatin and etoposide;
   6. 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 – 6 months or duration of request, whichever is less I. Other diagnoses/indications (must meet 1 or 2):
9. 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
10. 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 1 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.
    II. Continued Therapy A. All Indications in Section I (must meet all):
11. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tecentriq for a covered indication and has received this medication for at least 30 days;

12. Member is responding positively to therapy;

    3. If request is for a dose increase, request meets one of the following (a or b):* a. New dose does not exceed one of the following (i or ii):
       i. For pediatric ASPS: 15 mg/kg (up to a maximum of 1,200 mg) every 3 weeks; ii. All other indications: 1,680 mg every 4 weeks; Page 5 of 12

    CLINICAL POLICY Atezolizumab b. New 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 – 12 months Commercial – 6 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

13. 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

14. 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 1 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 policy – 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 ALK: anaplastic lymphoma kinase ASPS: alveolar soft part sarcoma EGFR: epidermal growth factor receptor ES-SCLC: extensive-stage small cell lung cancer FDA: Food and Drug Administration HCC: hepatocellular carcinoma IC: immune cells NSCLC: non-small cell lung cancer PD-L1: programmed death-ligand 1 SCLC: small cell lung cancer TC: tumor cells
    UC: urothelial 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 and may require prior authorization.
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    CLINICAL POLICY Atezolizumab Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies UC: Varies NSCLC: Varies cisplatin-, oxaliplatin- (Eloxatin®) or carboplatin-containing chemotherapy cisplatin-, or carboplatin-containing chemotherapy Xalkori® (crizotinib) Alecensa® (alectinib) Zykadia® (ceritinib) erlotinib (Tarceva®) Gilotrif® (afatinib) gefitinib (Iressa®) 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. NSCLC with ALK tumor aberration: Varies NSCLC with EGFR tumor aberration: Varies Varies Varies Varies Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • NSCLC examples of high-risk factors: may include poorly differentiated tumors (including lung neuroendocrine tumors [excluding well-differentiated neuroendocrine tumors]), vascular invasion, wedge resection, visceral pleural involvement, and unknown lymph node status (Nx). These factors independently may or may not be an indication and may be considered when determining treatment with adjuvant chemotherapy. • SCLC consists of two stages: limited-stage and extensive-stage. Extensive-stage is defined as stage IV (T any, N any M 1a/b) or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. • On December 2, 2022, following consultation with the FDA, Roche withdrew Tecentriq’s use for any form of UC. The withdrawal was based on data from the IMVigor130 study, which tested Tecentriq with chemotherapy against chemotherapy alone and failed to meet the co-primary endpoint of overall survival. Patients given Tecentriq chemo combination lived a median of 16 months after treatment, compared with 13.4 months for those receiving just chemo, a difference that wasn’t statistically significant.
    V. Dosage and Administration
    Indication NSCLC Dosing Regimen In the adjuvant setting: administer Tecentriq following resection and up to 4 cycles of platinum- based chemotherapy as 840 mg IV every 2 weeks, 1,200 mg IV every 3 weeks, or 1,680 mg IV every 4 weeks for up to 1 year In the metastatic setting: administer Tecentriq as 840 mg IV every 2 weeks, 1,200 mg IV every 3 weeks, or 1,680 mg IV every 4 weeks Maximum Dose 1,680 mg/4 weeks Page 7 of 12

    CLINICAL POLICY Atezolizumab Indication Dosing Regimen Maximum Dose SCLC HCC Melanoma ASPS When administering with chemotherapy with or without bevacizumab, administer Tecentriq prior to chemotherapy and bevavizumab when given on the same day 840 mg IV every 2 weeks, 1,200 mg IV every 3 weeks, or 1,680 mg IV every 4 weeks. When administering with carboplatin and etoposide, administer Tecentriq prior to chemotherapy when given on the same day.
    840 mg IV every 2 weeks, 1,200 mg IV every 3 weeks, or 1,680 mg IV every 4 weeks. Administer Tecentriq prior to bevacizumab when given on the same day. Bevacizumab is administered at 15 mg/kg every 3 weeks.
    Following completion of a 28 day cycle of cobimetinib and vemurafenib, administer Tecentriq 840 mg IV every 2 weeks, 1,200 mg every 3 weeks, or 1680 mg every 4 weeks with cobimetinib 60 mg PO QD (21 days on/7 days off) and vemurafenib 720 mg PO BID Adults: 840 mg IV every 2 weeks, 1,200 mg IV every 3 weeks, or 1,680 mg IV every 4 weeks 1,680 mg/4 weeks 1,680 mg/4 weeks 1,680 mg/4 weeks Adults: 1,680 mg/4 weeks Pediatrics: 15 mg/kg (up to a maximum of 1,200 mg) every 3 weeks
    Pediatrics: 1,200 mg/3 weeks VI. Product Availability
    Single-dose vials: 840 mg/14 mL, 1,200 mg/20 mL VII.