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Atezolizumab (Tecentriq®)
MA08.127b

Policy

MEDICALLY NECESSARY​

​HEPATOCELLULAR CARCINOMA ​(HCC)
Atezolizumab (Tecentriq) is considered medically necessary and, therefore, covered as a first-line system​ic therapy in combination with bevacizumab (National Comprehensive Cancer Network [​NCCN​]-preferred regimen) for the treatment of individuals with hepatocellular carcinoma (Child-Pugh Class A only) with any of the following:
  • Unresectable disease and not a transplant candidate
  • ​​Liver-confined disease, inoperable by Eastern Cooperative Oncology Group (ECOG) Performance Status ​(PS), or comorbidity, or with minimal or uncertain extrahepatic disease​​
  • Metastatic disease or extensive liver tumor burden
MELANOMA
Atezolizumab (Tecentriq) is considered medically necessary and, therefore, covered in combination with cobimetinib and vemurafenib for the first-line treatment of individuals with proto-oncogene B-Raf ​(BRAF) V600 mutation-positive unresectable or metastatic melanoma (includes stage III unresectable/borderline resectable disease with clinically positive node(s) or clinical satellite/in-transit metastases or unresectable local satellite/in-transit recurrence, unresectable nodal recurrence, and widely disseminated distant metastatic disease)​​

NON-SMALL CELL LUNG CANCER (NSCLC)
Initial Therapy for NSCLC

Atezolizumab (Tecentriq) is considered medically necessary and, therefore, covered for the treatment of individuals with recurrent (excluding locoregional recurrence or symptomatic local disease with no evidence of disseminated disease; however, including mediastinal lymph node recurrence with prior radiation therapy [RT]), advanced or metastatic non-small cell lung cancer (NSCLC) in any of the following regimens:
  • ​First-line systemic therapy (NCCN preferred) when ​all of the following criteria are met​​:
    •  PD-L1 expression positive (50 percent or greater or PD-L1 stained tumor-infiltrating immune cells [IC] covering 10 percent or greater of the tumor area [IC 10 percent or greater]) tumors (as determined by a FDA-approved test)​ that are epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), BRAF, neurotrophic tyrosine kinase receptor (NTRK) 1/2/3, mesenchymal-epithelial transition (MET) exon 14 skipping mutation, and rearranged during transfection (RET) negative​*
    • No contraindications​** to Programmed Death-1 (​PD-1) or PD-L1 inhibitors 
    • PS 0-2
  • First-line systemic therapy when​​ ​all of the following criteria are met:
    • ​In combination with either of the following regimens:
      • Bevacizumab, carboplatin, and paclitaxel (if no history of recent hemoptysis)
      • Carboplatin and albumin-bound paclitaxel
    • ​PD-L1 expression positive (1 percent or greater) tumors that are EGFR, ALK, ROS1, BRAF, NTRK 1/2/3, MET, and RET negative​*
    • No contraindications​​** to PD-1 or PD-L1 inhibitors
    • PS 0-2
    • Non-squamous cell history
  • ​​​​​​Single-agent as subsequent therapy (NCCN preferred) when both of the following criteria are met:
    • ​PS 0-2
    • No prior progression on a PD-1 or PD-L1 inhibitor​​​​
  • ​Combination systemic therapy with carboplatin, paclitaxel, and bevacizumab (if no history of recent hemoptysis), or in combination with carboplatin and albumin-bound paclitaxel, for the treatment of individuals with PS 0-1, no contraindications​** to PD-1 or PD-L1 inhibitors, and tumors of non-squamous cell histology in any of the following regimens:
    • Initial systemic therapy for EGFR, ALK, ROS1, BRAF, NTRK 1/2/3, MET, and RET negative​* and PD-L1 expression positive ​(<1 percent) tumors​
    • First-line therapy for EGFR exon 20 mutation positive* tumors
    • First-line therapy for KRAS G12C mutation positive* tumors​
    • First-line or subsequent therapy for B​​RAF V600E-mutation positive​* tumors
    • First-line or subsequent therapy for NTRK 1/2/3 gene fusion positive​* tumors
    • First-line or subsequent therapy for MET exon 14 skipping mutation positive​​*​ tumors
    • First-line or subsequent therapy for RET rearrangement positive* tumors
    • Subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation positive tumors* and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy​
    • Subsequent systemic therapy for ROS1 rearrangement-positive​* tumors and prior crizotinib, entrectinib, or ceritinib therapy
  • For the treatment of individuals with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on a FDA-approved therapy for NSCLC harboring these aberrations prior to receiving atezolizumab (Tecentriq)​
  • As adjuvant treatment following resection and platinum-based chemotherapy for individuals with Stage IIB to IIIA or high-risk stage IIA NSCLC whose tumors have PD-L1 expression on 1 percent or greater of tumor cells, as determined by a FDA-approved test 
​​*If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK 1/2/3, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these individuals​ are treated as though they do not have driver oncogenes.

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (ie, EGFR [ exon 19 deletions or L858R, ALK rearrangements)​, which would predict lack of benefit.​

Continuation Therapy for NSCLC​

Atezolizumab (Tecentriq) is considered medically necessary and, therefore, covered for continuation therapy for the treatment of individuals with NSCLC, recurrent (excluding locoregional recurrence or symptomatic local disease with no evidence of disseminated disease; however, including mediastinal lymph node recurrence with prior RT), advanced, or metastatic disease in any of the following:
  • For PD-L1 expression positive (< 1 percent) tumors for tumor response or stable disease following first-line systemic combination therapy with atezolizumab (Tecentriq), carboplatin and albumin-bound paclitaxel with ​all of the following:
    • ​No contraindications** to PD-1 or PD-L1 inhibitors​
    • PS 0-2
    • Non-squamous cell histology
  • In combination with bevacizumab for PD-L1 expression positive (<1 percent) tumors for tumor response or stable disease following first-line systemic combination therapy with atezolizumab (Tecentriq), carboplatin, paclitaxel, and bevacizumab with all of the following:
    • No contraindications** to PD-1 or PD-L1 inhibitors
    • PS 0-2
    • Non-squamous cell histology
    • No history of recent hemoptysis​
  • In combination with bevacizumab for PD-L1 expression positive (1 percent or greater) tumors that are EGFR, ALK, ROS1, BRAF, NTRK 1/2/3, MET exon 14 skipping mutation, and RET​* negative ​​with all of the following: ​
    • Tumor response or stable disease following first-line systemic combination therapy with atezolizumab (Tecentriq), carboplatin, paclitaxel, and bevacizumab
    • No contraindications​** to PD-1 or PD-L1 inhibitors
    • PS 0-2
    • Non-squamous cell histology
    • ​​No history of recent hemoptysis​
  • For PD-L1 expression positive (1 percent or greater) tumors that are EGFR, ALK, ROS1, BRAF, NTRK 1/2/3, MET exon 14 skipping mutation, and RET​* negative with ​all of the following:
    • Tumor response or stable disease following first-line systemic combination therapy with atezolizumab (Tecentriq), carboplatin, and albumin-bound paclitaxel
    • No contraindications​** to PD-1 or PD-L1 inhibitors
    • PS 0-2
    • Non-squamous cell history 
  • For PD-L1 expression positive (50 percent or greater) tumors that are EGFR, ALK, ROS1, BRAF, NTRK 1/2/3,​ MET exon 14 skipping mutation, and RET​* negative with ​all of the following:
    • Tumor response or stable disease following first-line therapy with single-agent atezolizumab (Tecentriq) 
    • No contraindications​** to PD-1 or PD-L1 inhibitors
    • PS 0-2
​*If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK 1/2/3, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes.

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, or presence of an oncogene (ie, EGFR [ exon 19 deletions or L858R, ALK rearrangements), which would predict lack of benefit.​

SMALL CELL LUNG CANCER (SCLC)
Atezolizumab (Tecentriq) is considered medically necessary and, therefore, covered for first-line systemic combination therapy with etoposide and carboplatin (followed by single-agent maintenance) for the treatment of individuals with extensive-stage* Small Cell Lung Cancer (NCCN-preferred regimen) and any of the following criteria:
  • Without localized symptomatic sites or brain metastases and good PS (0-2)
  • Without localized symptomatic sites or brain metastases and poor PS (3-4) due to SCLC
  • Localized symptomatic sites
  • Brain metastases
*Extensive stage: Stage IV (T any, N any, M 1a/b), or T3-4 due to multiple lung nodules that are too extensive or tumor/nodule volume that is too large to be encompassed in a tolerable radiation plan (American Joint Committee on Cancer, 7th edition).

UROTHELIAL CARCINOMA
Atezolizumab (Tecentriq) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of individuals with any of the following urothelial carcinomas:
  • Locally advanced or metastatic urothelial carcinoma in ​either of the following:   
    • ​​​​Not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering greater than or equal to 5 percent of the tumor area) as determined by a FDA-approved test
    • Not eligible for any platinum-containing chemotherapy regardless of PD-L1 status
  • Primary carcinoma of the urethra, locally advanced or metastatic ​for either of the following:
    • Clinical stage T3-4, cN1-2 disease or cN1-2 palpable inguinal lymph nodes as primary treatment as first-line systemic therapy (NCCN-preferred regimen) in cisplatin-ineligible individuals whose tumors express PD-L1 or individuals who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression​*
    • Clinical stage not recurrent T3-4 disease and without palpable inguinal lymph nodes as first-line systemic therapy (NCCN-preferred regimen) in cisplatin-ineligible individuals and whose tumors express PD-L1 or in individuals who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression*
  • Bladder cancer, locally advanced or metastatic disease as first-line systemic therapy, (NCCN-preferred regimen) in cisplatin-ineligible individuals and whose tumors express PD-L1 or in individuals who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression, for the treatment of any of the following clinical stages:
    • Cystectomy candidates with stage II (cT2, N0) disease if tumor is present following reassessment of tumor status two to three months after primary treatment with bladder-preserving concurrent chemoradiotherapy
    • Non-cystectomy candidates with stage II (cT2, N0) disease if tumor is present following reassessment of tumor status two to three months after primary treatment 
    • Stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status two to three months after primary treatment with bladder-preserving concurrent chemoradiotherapy
    • Non-cystectomy candidates with stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present upon reassessment of tumor status two to three months after primary treatment
    • Stage IIIB (cT1-T4a, N2,3) disease as downstaging systemic therapy
    • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with concurrent chemoradiotherapy
    • Stage IVA (cT4b, any N, M0; any T, any N, M1a) disease 
    • Stage IVA (cT4b, and N, M0) disease as consolidation therapy if no tumor present following reassessment of tumor status two to three months after primary treatment with concurrent chemoradiotherapy
    • Stage IVA (cT4b, any N, M0) disease if tumor present following reassessment of tumor status two to three months after primary treatment with concurrent chemoradiotherapy​
    • Metastatic stage IVB (any T, any N, M1b) disease
    • Muscle invasive local recurrence or persistent disease in a preserved bladder
    • Metastatic or local recurrence post cystectomy
  • Urothelial carcinoma of the prostate for metastatic disease as first-line systemic therapy (NCCN-preferred regimen) in cisplatin-ineligible individuals and whose tumors express PD-L1 or in individuals who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression
  • Metastatic upper genitourinary tract tumors as first-line systemic therapy (NCCN-preferred regimen) in cisplatin-ineligible individuals and whose tumors express PD-L1 or in individuals who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression
*Chemotherapy regimen based on histology

​​EXPERIMENTAL/INVESTIGATIONAL

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

REQUIRED DOCUMENTATION

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

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

Guidelines

​There is no Medicare coverage determination addressing atezolizumab (Tecentriq); therefore, the Company policy is applicable.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when atezolizumab (Tecentriq) is covered under a member's medical benefit (Part B benefit). It does not address instances when atezolizumab (Tecentriq) is covered under a member's pharmacy benefit (Part D benefit).

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, atezolizumab (Tecentriq) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern United States to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.

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

THE CHILD-PUGH SCORE 

Note: The Child-Pugh score is calculated by adding the scores of the five factors and can range from 5 to 15. Child-Pugh class is A (a score of 5-6), B (7-9), or C (10 or above). Decompensation indicates cirrhosis with a Child-Pugh score of 7 or more (class B). This level has been the accepted criterion for listing for liver transplantation.
Factor
Units
1
2
3
Serum bilirubin
mmol/L

mg/dL
< 34

< 2.0
34-51

2.0-3.0
>51

>3.0
Serum albumin
g/L

g/dL
>35

>3.5
30-35

3.0-3.5
< 30

< 3.0
Prothrombin time
Seconds prolonged

INR
0-4

< 1.7
4-6

1.7-2.3
>6

>2.3
Ascites
None
Easily controlled
Poorly controlled
Hepatic encephalopathy
None
Minimal
Advanced
Note: Table 163-3: Child-Pugh Classification of Cirrhosis : In Harrison's Manual of Medicine 17th ed.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Atezolizumab (Tecentriq) was approved by the FDA on May 18, 2016 for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who either have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Supplemental approvals for atezolizumab (Tecentriq) have since been issued by the FDA. Atezolizumab (Tecentriq) is administered as an intravenous infusion over 60 minutes.

Refer to the atezolizumab (Tecentriq) prescribing information for further information on FDA-approved tests for determining Programmed Death-1 (PD-1), Programmed Death-Ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), proto-oncogene B-Raf (BRAF), neurotrophic tyrosine kinase receptor (NTRK) 1/2/3, mesenchymal-epithelial transition (MET) exon 14 skipping mutation, and rearranged during transfection (RET) expression.

PEDIATRIC USE
The safety and effectiveness of atezolizumab (Tecentriq) have not been established in pediatric individuals.​​

Description

In a normal immune response, the body can recognize the presence of tumors and mount a response to eradicate them. The process of eradicating a tumor begins with antigen-presenting cells that gather and process the antigens released by tumors. This activates the T-cells, which proliferate and attack the tumor.

Tumors have learned to evade the normal immune response by exploiting the immune checkpoint pathway. The Programmed Death Receptor-1 (PD-1) is a checkpoint protein expressed on the membrane of activated T-cells. The Programmed Death-Ligand 1 (PD-L1) and the Programmed Death-Ligand 2 (PD-L2) are checkpoint proteins expressed on tumor cells and tumor-infiltrating immune cells. When PD-L1 and PD-L2 attach to PD-1 receptors on the T-cells, the T-cells become inhibited and will not attack the tumor; thus, the tumor can continue to proliferate.

Atezolizumab (Tecentriq) is a human monoclonal antibody and immune checkpoint inhibitor that binds to PD-L1 on tumor cells and tumor-infiltrating immune cells and blocks the interaction with PD-1 and B7.1 receptors on T-cells and antigen-presenting cells. Consequently, the tumor is no longer able to inactivate the T-cells, and the antitumor response continues. 

ATEZOLIZUMAB (TECENTRIQ) INDICATIONS

HEPATOCELLULAR CARCINOMA (HCC)
Hepatocellular carcinoma (HCC), the most common type of cancer in the liver, gallbladder, and bile ducts, is usually diagnosed at an advanced stage and is the third leading cause of cancer-related deaths worldwide.

In May 2020, the US Food and Drug Administration (FDA)​ approved atezolizumab (Tecentriq) in combination with bevacizumab (Avastin®​) for individuals with unresectable or metastatic HCC who had not received prior systemic therapy. Efficacy was investigated in IMbrave150 (NCT03434379), a multicenter, international, open-label, randomized trial in individuals with locally advanced unresectable or metastatic HCC who had not received prior systemic therapy. A total of 501 individuals were randomized (2:1) to receive either atezolizumab (Tecentriq) 1200 mg as an intravenous infusion (IV) followed by bevacizumab 15 mg/kg IV on the same day, every three weeks, or sorafenib orally twice daily. The main efficacy outcome measures were overall survival (OS) and independent review facility (IRF)-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Additional efficacy outcome measures were IRF-assessed objective response rate (ORR) per RECIST v1.1 and modified RECIST (mRECIST). Median OS was not reached in the individuals who received atezolizumab (Tecentriq)​ plus bevacizumab and was 13.2 months (95 percent confidence interval (CI) 10.4 to not estimable [NE]) in the individuals who received sorafenib (hazard ration [HR] 0.58; 95 percent CI 0.42 to 0.79; p=0.0006). Median PFS was 6.8 months (95 percent CI 5.7 to 8.3) versus 4.3 months (95 percent CI 4.0 to 5.6), respectively (HR 0.59; 95 percent CI 0.47 to 0.76; p<0.0001). The ORR per RECIST v1.1 was 27.3 percent (95 percent CI 22.5 to 32.5) in the atezolizumab (Tecentriq) plus bevacizumab group compared with 11.9 percent (95 percent CI 7.4 to 18.0) in the sorafenib group (p<0.0001). The ORR per mRECIST was 33.2 percent (95 percent CI 28.1 to 38.6) versus 13.3 percent (95 percent CI 8.4 to 19.6), respectively (p<0.0001).​ The most common adverse reactions (reported in 20 percent or greater of individuals) with atezolizumab (Tecentriq) plus bevacizumab in individuals with HCC were hypertension, fatigue, and proteinuria.

MELANOMA
Melanoma tumors are made of abnormal melanocytes that have become cancer cells. Melanoma is much less common than some other types of skin cancers. But melanoma is more dangerous because it is much more likely to spread to other parts of the body if not caught and treated early.

In July 2020, the FDA approved atezolizumab (Tecentriq) in combination with cobimetinib and vemurafenib for individuals with proto-oncogene B-Raf (BRAF) V600 mutation-positive unresectable or metastatic melanoma. The efficacy of atezolizumab (Tecentriq) in combination with cobimetinib and vemurafenib was evaluated in a phase III, double-blind, randomized (1:1), placebo-controlled, multicenter trial (IMspire150; NCT02908672) conducted in 514 individuals. Eligible individuals were required to have previously untreated unresectable or metastatic BRAF V600 mutation-positive melanoma. Individuals were enrolled and randomly assigned to the atezolizumab (Tecentriq) group (n=256) or control group (n=258). At a median follow-up of 18.9 months (interquartile range [IQR] 10.4 to 23.8), PFS as assessed by the study investigator was significantly prolonged with atezolizumab (Tecentriq) versus control (15.1 versus 10.6 months; [HR] 0.78; 95 percent CI 0.63 to 0.97; p=0.025).  The addition of atezolizumab (Tecentriq) to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased PFS in individuals with BRAF V600 mutation-positive advanced melanoma.

NON-SMALL CELL LUNG CANCER (NSCLC)
Lung cancer is the leading cause of cancer-related mortality in both men and women, not only in the United States but also throughout the world. In the United States, lung cancer is the second most common cancer. NSCLC accounts for approximately 85 percent of all lung cancers, and its subtype, squamous cell lung cancer, accounts for 25 to 30 percent of all lung cancers. 

In October 2016, the FDA granted supplemental approval of atezolizumab (Tecentriq) for the treatment of individuals with metastatic NSCLC whose disease progressed during or following platinum-containing chemotherapy. Individuals with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase​ (ALK) genomic tumor aberrations should have disease progression on a FDA-approved therapy for these aberrations prior to receiving atezolizumab (Tecentriq).

The safety of atezolizumab (Tecentriq) was evaluated in a multi-center, international, randomized, open-label trial in individuals with metastatic NSCLC who progressed during or following a platinum-containing regimen, regardless of PD-L1 expression. The FDA approval of atezolizumab (Tecentriq) for metastatic NSCLC was based on results from Phase III and Phase II studies. The Phase III study enrolled 1,225 individuals who were randomized 1:1 ratio to receive either docetaxel (75mg/m2) or atezolizumab (Tecentriq) 1200 mg IV every three weeks. Results from the Phase III indicates that atezolizumab (Tecentriq) helped individuals in the overall study population live a median of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy. The Phase II study enrolled 287 individuals and the study showed that atezolizumab (Tecentriq) doubled the likelihood of survival in individuals whose cancer expressed the highest levels of PD-L1 compared with docetaxel chemotherapy. An improvement in survival was also observed in individuals who had medium and high or any level of PD-L1 expression.

On December 2018, atezolizumab (Tecentriq) also received the FDA-approved indication of NSCLC, in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adult individuals with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. The safety and efficacy of atezolizumab (Tecentriq) with bevacizumab, paclitaxel, and carboplatin was evaluated in IMpower150 (NCT02366143), a multicenter, international, randomized, open-label trial in 1202 individuals with metastatic non-squamous NSCLC. Three hundred ninety-three chemotherapy-naïve individuals with metastatic non-squamous NSCLC received atezolizumab (Tecentriq) 1200 mg with bevacizumab 15 mg/kg, paclitaxel 175 mg/m2 or 200 mg/m2, and carboplatin area under the curve (AUC) 6 mg/mL/min every ​three weeks for a maximum of ​four or ​six cycles, followed by atezolizumab (Tecentriq) 1200 mg with bevacizumab 15 mg/kg every three weeks until disease progression or unacceptable toxicity. The median duration of exposure to atezolizumab (Tecentriq) was 8.3 months in individuals receiving atezolizumab (Tecentriq) with bevacizumab, paclitaxel, and carboplatin.

On December 2019, the FDA approved atezolizumab (Tecentriq) for the first-line treatment of adult individuals with metastatic non-squamous NSCLC with no EFGR or ALK genomic tumor aberrations, in combination with albumin-bound paclitaxel and carboplatin. This was based on a multicenter, randomized, open-label trial in individuals with stage IV non-squamous NSCLC. Individuals were randomized to one of the following treatment regimens: atezolizumab (Tecentriq), albumin-bound paclitaxel, and carboplatin for a maximum of ​four or six cycles followed by atezolizumab (Tecentriq) until disease progression or unacceptable toxicity, or albumin-bound paclitaxel and carboplatin for a maximum of four or six cycles followed by best supportive care or pemetrexed. Major efficacy outcome measures were PFS by RECIST v1.1 and OS in the subpopulation of individuals evaluated for and documented to have no EGFR or ALK genomic tumor aberrations intention to treat-wild type ​(ITT-WT). A total of 724 individuals were enrolled; of these, 681 (94 percent) were in the ITT-WT population. Baseline Eastern Cooperative Oncology Group (​ECOG) Performance Status ​(PS) was 0 (41 percent) or 1 (58 percent). Fifty percent of individuals treated with atezolizumab (Tecentriq) died compared to 57 percent treated with placebo (HR 0.80 95 percent CI 0.64 to 0.99, p=0.0384). The duration of response was 10.8 months in the atezolizumab (Tecentriq) group compared to 7.8 months in the placebo group.

In May 2020, the FDA approved atezolizumab (Tecentriq)  for the first-line treatment of adult individuals with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained 50 percent or greater of tumor cells [TC] [TC 50 percent or greater] or PD-L1 stained tumor-infiltrating immune cells [IC] covering 10 percent or greater of the tumor area [IC 10 percent or greater), with no EGFR or ALK genomic tumor aberrations. Efficacy was evaluated in IMpower110 (NCT02409342), a multicenter, international, randomized, open-label trial in individuals with stage IV NSCLC whose tumors express PD-L1 (TC 1 percent or greater or IC 1 percent or greater), who had received no prior chemotherapy for metastatic disease. Individuals were randomized (1:1) to receive atezolizumab (Tecentriq) 1200 mg every ​​three weeks until disease progression or unacceptable toxicity or platinum-based chemotherapy. The main efficacy outcome measure was OS. The trial demonstrated a statistically significant improvement in OS for individuals with high PD-L1 tumor expression receiving atezolizumab (Tecentriq) compared to those treated with platinum-based chemotherapy. Median OS was 20.2 months (95 percent CI 16.5 to NE) for individuals in the atezolizumab (Tecentriq) arm compared with 13.1 months (95 percent CI 7.4 to 16.5) in the chemotherapy arm (HR 0.59; 95 percent CI 0.40 to 0.89; p=0.0106). There was no statistically significant difference in OS for the other two PD-L1 subgroups (TC 5 percent or greater or IC 5 percent or greater; and TC 1 percent or greater or IC 1 percent or greater) at the interim or final analyses. Median PFS per investigator was 8.1 months (95 percent CI 6.8 to 11.0) in the atezolizumab (Tecentriq) arm and 5.0 months (95 percent CI 4.2 to 5.7) in the platinum-based chemotherapy arm (HR 0.63; 95 percent CI 0.45 to 0.88). Confirmed ORR per investigator was 38 percent (95 percent CI 29 to 48) and 29 percent (95 percent CI 20 to 39), respectively.

SMALL CELL LUNG CANCER (SCLC)
Small cell lung cancer (SCLC), previously known as oat cell carcinoma, is considered distinct from other lung cancers, which are called NSCLCs because of their clinical and biologic characteristics. SCLC is a neuroendocrine carcinoma that exhibits aggressive behavior, rapid growth, early spread to distant sites, sensitivity to chemotherapy and radiation, and frequent association with distinct paraneoplastic syndromes.

In March 2019, the FDA approval of atezolizumab (Tecentriq) for the first-line treatment of adult individuals with extensive-stage SCLC, with carboplatin and etoposide. This was based on a randomized, multicenter, double-blind, placebo-controlled trial in 403 individuals with extensive-stage SCLC. Individuals were randomized to atezolizumab (Tecentriq) in combination with carboplatin and etoposide or placebo in combination with carboplatin and etoposide. The major efficacy outcome measures were OS and PFS as assessed by investigator in the ITT population. Fifty-two percent of individuals treated with atezolizumab (Tecentriq) died compared to those treated with placebo (HR 0.70 95 percent CI 0.54 to 0.91, p=0.0069). The duration of response was 4.2 months in the atezolizumab (Tecentriq) group compared to 3.9 months in placebo group.

UROTHELIAL CANCER
The urinary tract is composed of the renal pelvis, ureters, bladder, and urethra. The innermost lining of the urinary tract is composed of urothelial cells. Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the ninth most common cancer overall worldwide and it accounts for 90 percent of all bladder cancers. Squamous cell carcinoma comprises one to seven percent of upper tract urothelial tumors. Adenocarcinoma accounts for less than one percent of upper tract tumors. Urothelial tumors of the renal pelvis and ureters are rare. Tumors of the renal pelvis account for approximately five percent of all urothelial tumors of the urinary tract.

In May 2016, the US Food and Drug Administration (FDA) gave accelerated approval of atezolizumab (Tecentriq) for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment, or in those individuals not eligible for cisplatin-containing chemotherapy. 

The safety and efficacy of atezolizumab (Tecentriq) were studied in a single-arm clinical trial involving 310 individuals with locally advanced or metastatic urothelial carcinoma. The trial measured the percentage of individuals who experienced complete or partial shrinkage of their tumors. The study also looked at the difference in effect based on PD-L1 expression positive versus PD-L1 expression negative tumors. In all individuals, 14.8 percent of individuals experienced at least a partial shrinkage of their tumors, an effect that lasted from more than 2.1 to more than 13.8 months at the time of the response analysis. In individuals who were classified as “positive" for PD-L1 expression, 26 percent of individuals experienced a tumor response (compared to 9.5 percent of individuals who were classified as “negative" for PD-L1 expression).

Atezolizumab (Tecentriq) received FDA approval for use in locally advanced or metastatic urothelial carcinoma in individuals who are not eligible for cisplatin-containing therapy. The FDA approval was based on a multicenter, open-label, single-arm trial that included 119 individuals with locally advanced or metastatic urothelial carcinoma who were ineligible for cisplatin. Individuals were considered ineligible for cisplatin therapy due to impaired renal function, ECOG PS of 2 or higher, hearing loss of >25 dB at two contiguous frequencies, or greater than grade 2 peripheral neuropathy. The ORR was 23.5 percent with 6.7 percent of individuals experiencing a complete response. The median duration of response has not been yet been reached. This additional indication was approved under an accelerated approval that was based on tumor response rate and durability of response in this population. Continued approval of this indication will be contingent upon verification and description of clinical benefit in a confirmatory trial.​

OFF-LABEL INDICATIONS
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.​​

References

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American Hospital Formulary Service (AHFS). Drug Information 2021. Atezolizumab (Tecentriq®). [Lexicomp Online Web site]. 11/12/2021. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed December 27, 2021.
   
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Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894-1905.​

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Coding

CPT Procedure Code Number(s)
N/A

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

ICD - 10 Diagnosis Code Number(s)
See Attachment A.

HCPCS Level II Code Number(s)

J9022 Injection, atezolizumab, 10 mg


Revenue Code Number(s)
N/A






Coding and Billing Requirements


Policy History

3/14/2022
3/14/2022
MA08.127
Medical Policy Bulletin
Medicare Advantage
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No