Coverage Policy Manual
Policy #: 2016016
Category: Pharmacy
Initiated: July 2016
Last Review: January 2019
  Atezolizumab (Tecentriq®)

Description:
Atezolizumab  (Tecentriq)   is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1) which acts on the PD-1/PD-L1 pathway (proteins found on the body's immune cells and some tumor cells). By blocking these co-ordinations, atezolizumab  may help the body's defense system to cope with tumor cells. Tecentriq is marketed by Genentech based in San Francisco, California. The Ventana PD-L1 (SP142) assay complementary diagnostic for Tecentriq is marketed by Ventana Medical Systems, based in Tucson, Arizona.
 
Atezolizumab  is reserved for the treatment of patients with locally progressed or metastatic urothelial carcinoma whose disease has become more severe after continuous administration of platinum-containing chemotherapy, or within range of 12 months of getting platinum-containing chemotherapy, either before (neoadjuvant) or after (adjuvant) surgical treatment. Urothelial carcinoma has high prevalence rate as compared to other type of bladder cancer. It takes place in the urinary system and spreads rapid to surrounding organs.
 
On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab (Tecentriq) to treat urothelial carcinoma. Atezolizumab is the first PD-1/PD-L inhibitor approved to treat this type of cancer. The FDA granted the application the breakthrough therapy designation, priority review status and accelerated approval for this indication.
 
On October 18, 2016, atezolizumab (Tecentriq) was approved for the treatment of metastatic NSCLC in patients who have disease progression during or following platinum-containing chemotherapy and have progressed on an appropriate FDA-approved targeted therapy if their tumors have epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene abnormalities. The approved indication is not limited by PD-L1 status.
 
On March 8, 2019, the U.S. Food and Drug Administration approved atezolizumab in combination with paclitaxel protein-bound for adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1 as determined by an FDA-approved test.
 
On March 18, 2019, the U.S. Food and Drug Administration approved atezolizumab in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer.

Policy/
Coverage:
Effective April 2019
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Atezolizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
 
    1. Urothelial Carcinoma
The treatment of patients 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 with platinum-containing chemotherapy   OR
        • are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor infiltrating immune cells (IC) covering >5% of the tumor area) OR
        • who are not eligible for any platinum containing chemotherapy regardless of PD-L1 status
2. Non-Small Cell Lung Cancer (NSCLS)
The treatment of patients with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy.  
        • 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.
        • 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 progression on FDA-approved therapy NSCLC harboring these aberrations prior to receiving TECENTRIQ.
       3. Triple-Negative Breast Cancer (TNBC)
        • In combination with paclitaxel protein-bound for the treatment of adult tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells of any intensity cover > 1% of the tumor area), as determined by an FDA approved test. This indication is approved under accelerated approval based on progression free survival. Continue approval of this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
       4. Small Cell Lung Cancer (SCLC)
        • In combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
 
Off Label
        • NCCN 1, 2A, and 2B Recommendations in accordance with Coverage Policy #2000030.
 
Dosage and administration:
 
Urothelial Carcinoma
        • TECENTRIQ 1200 mg intravenously over 60 minutes every 3 weeks.
 
NSCLC
        • TECENTRIQ 1200 mg intravenously over 60 minutes every 3 weeks. If administering in combination, administer TECENTRIQ prior to chemotherapy or other antineoplastic drugs when administered on the same day.
 
Metastatic Treatment of TNBC
        • TECENTRIQ 840 mg IV over 60 minutes, followed by 100 mg/m2 paclitaxel protein-bound. For each 28 day cycle, TECENTRIQ is administered on days 1 and 15, and paclitaxel protein-bound is administered on days 1, 8, and 15.
 
Small Cell Lung Cancer
        • TECENTRIQ 1200 mg intravenously over 60 minutes every 3 weeks. When administering in combination, administer TECENTRIQ prior to chemotherapy when administered on the same day.
 
If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
 
 Does Not Meet Primary Coverage Criteria or Is Investigational for Contracts Without Primary Coverage Criteria
 
Atezolizumab does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any other indication that does not meet primary coverage criteria and is not covered including but not limited to:
 
 
        • First line therapy for urothelial carcinoma at any stage
        • Treatment of renal cell carcinoma at any stage
        • First line therapy for non-small cell lung cancer at any stage, except in adult patients with extensive-stage small cell lung cancer (ES-SCLC).
        • Treatment of melanoma at any stage
 
For members with contracts without primary coverage criteria, atezolizumab is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective 1/17/2019 to March 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Atezolizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
    • The treatment of patients with locally advanced or metastatic urothelial carcinoma who:
        1. Have disease progression during or following platinum-containing chemotherapy, OR   
        2. Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy   OR
        3. are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor infiltrating immune cells (IC) covering >5% of the tumor area) OR
        4. who are not eligible for any platinum containing chemotherapy regardless of PD-L1 status
    • Metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy.  
        • Note: Patients with EGFR or ALK genomic tumor aberrations should have disease progression on an FDA approved targeted therapy for the appropriate genetic abnormality. The approved indication is not limited by PD-L1 status.
 
Dosage and administration:
FDA dosing is atezolizumab 1200 mg IV every 3 weeks until disease progression or development of a drug limiting adverse effect.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Off Label
    • NCCN 1, 2A, and 2B Recommendations in accordance with Coverage Policy #2000030.
 
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Atezolizumab does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any other indication that does not meet primary coverage criteria and is not covered including but not limited to:
 
    • First line therapy for urothelial carcinoma at any stage
    • Treatment of renal cell carcinoma at any stage
    • First line therapy for non-small cell lung cancer at any stage
    • Treatment of melanoma at any stage
 
For members with contracts without primary coverage criteria, atezolizumab is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 2018 - January 16, 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Metastatic Urothelial Carcinoma
Atezolizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
  • The treatment of patients with locally advanced or metastatic urothelial carcinoma who:
        1. Have disease progression during or following platinum-containing chemotherapy, OR   
        2. Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy   OR
        3. are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor infiltrating immune cells (IC) covering >5% of the tumor area) OR
        4. who are not eligible for any platinum containing chemotherapy regardless of PD-L1 status
  • Metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy.  
  • Note: Patients with EGFR or ALK genomic tumor aberrations should have disease progression on an FDA approved targeted therapy for the appropriate genetic abnormality. The approved indication is not limited by PD-L1 status.
  • NCCN 2A and 2B Recommendations in accordance with Coverage Policy #2000030.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Atezolizumab does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any other indication that does not meet primary coverage criteria and is not covered including but not limited to:
 
              • First line therapy for urothelial carcinoma at any stage
              • Treatment of renal cell carcinoma at any stage
              • First line therapy for non-small cell lung cancer at any stage
              • Treatment of melanoma at any stage
 
For members with contracts without primary coverage criteria, atezolizumab is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Dosage and administration:
FDA dosing is atezolizumab 1200 mg IV every 3 weeks until disease progression or development of a drug limiting adverse effect.
 
Effective September 2017
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Metastatic Urothelial Carcinoma
The use of atezolizumab meets primary coverage criteria for the treatment of patients with locally advanced or metastatic urothelial carcinoma with one of the following:
 
    1. Disease progression during or following platinum-containing chemotherapy, OR   
    2. Disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy  
 
Non-Small Cell Lung Cancer
The use of atezolizumab meets primary coverage criteria for the treatment of patients with non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy.
 
Note: Patients with EGFR or ALK genomic tumor aberrations should have disease progression on an FDA approved targeted therapy for the appropriate genetic abnormality. The approved indication is not limited by PD-L1 status.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of atezolizumab for any other indication does not meet primary coverage criteria and is not covered including but not limited to:
 
        1. First line therapy for urothelial carcinoma at any stage
        2. Treatment of renal cell carcinoma at any stage
        3. First line therapy for non-small cell lung cancer at any stage
        4. Treatment of melanoma at any stage
 
For members with contracts without primary coverage criteria, the use of atezolizumab for any other indication, including but not limited to, those listed above, are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Policy Guidelines:
 
Approved dosage for atezolizumab is 1200 mg IV every 3 weeks until disease progression or development of a drug limiting adverse effect.
 
EFFECTIVE PRIOR TO SEPTEMBER 2017
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of atezolizumab meets primary coverage criteria for the treatment of patients with locally advanced or metastatic urothelial carcinoma with one of the following:
 
    1. Disease progression during or following platinum-containing chemotherapy, OR  
    2. Disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of atezolizumab for any other indication does not meet primary coverage criteria and is not covered including but not limited to:
 
    1. First line therapy for urothelial carcinoma at any stage
    2. Treatment of renal cell carcinoma at any stage
    3. Treatment of non-small cell lung cancer at any stage
    4. Treatment of melanoma at any stage
 
For members with contracts without primary coverage criteria, the use of atezolizumab for any other indication, including but not limited to, those listed above, are considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Policy Guidelines:
 
Approved dosage for atezolizumab is 1200 mg IV every 3 weeks until disease progression or development of a drug limiting adverse effect.

Rationale:
In cohort 1 of the phase II study, atezolizumab was used as first-line therapy in 119 patients with advanced or metastatic urothelial carcinoma who were not eligible for treatment with a cisplatin-based regimen. The objective response rate was 26 percent, including 7 percent of patients with a complete response. Objective responses, as assessed by independent review, were observed in 45 cases (15 percent). At a median follow-up of 12 months, 38 of 45 (84 percent) responses were ongoing.  Response data were analyzed based upon expression of PD-L1. Although the response rates were higher in those with more expression of PD-L1 on infiltrating immune cells, objective responses were sometimes observed even in those with no expression of PD-L1.
 
The safety profile was similar to that in cohort 2. Although the majority of patients who were included had preexisting renal impairment, treatment was well tolerated, and there was no evidence of any nephrotoxicity. There was no correlation with immunohistochemical expression of PD-L1.
 
Results of a phase III trial (NCT02302807) that is currently ongoing comparing atezolizumab with second-line chemotherapy will be required to confirm the role of atezolizumab to treat urothelial carcinoma.
 
2017 Update
In the OAK Trial (Rittmeyer et al., 2017) trial randomized 850 patients (primary efficacy population) with stage IIIB or IV NSCLC to receive either intravenous atezolizumab 1200 mg (n=425) or chemotherapy with docetaxel 75 mg/m² (n=425) once every 3 weeks until disease progression or unacceptable toxicity. All patients had disease that had progressed following at least 1 previous course of platinum-based chemotherapy; 222 (26%) had squamous and 628 (74%) had nonsquamous NSCLC.  The trial was designed to initially enroll 850 patients; the sample size was later expanded to power for an OS comparison in patients with high PD-L1 expression. A total of 1225 patients were ultimately randomized; 609 received atezolizumab and 578 received docetaxel (safety population).  The primary endpoint was OS in the intention-to-treat (ITT) population and in the PD-L1 TC1/2/3 or IC1/2/3 populations (patients with TCs or ICs with PD-L1 expression 1%). This endpoint significantly favored atezolizumab  over docetaxel in both populations. At median follow-up of 21 months, OS in the ITT population was significantly prolonged by 4.2 months among patients treated with atezolizumab compared with docetaxel (13.8 and 9.6 months, respectively; P=0.0003). OS in the TC1/2/3 or IC1/2/3 population was also significantly prolonged in patients treated with atezolizumab( n=241) compared with docetaxel (n=222); median OS was 15.7 months and 10.3 months, respectively (P=0.0102). Progression-free survival (PFS), a secondary endpoint, was statistically similar between the 2 groups.
 
In the POPLAR Trial (Fehrenbacher et al., 2016) trial randomized patients with previously treated advanced NSCLC to receive either intravenous atezolizumab 1200 mg (n=144) or docetaxel 75 mg/m² (n=143) once every 3 weeks. All patients had disease that had progressed following platinum-based chemotherapy. Of the 287 patients randomized, 97 (34%) had squamous NSCLC and 190 (66%) had nonsquamous NSCLC.  The primary efficacy endpoint of median OS was significantly prolonged among patients treated with co atezolizumab mpared with docetaxel (12.6 and 9.7 months, respectively; P=0.040). PFS, a secondary endpoint, was statistically similar between the 2 groups (2.7 months with atezolizumab and 3.0 months with docetaxel). An OS advantage with , atezolizumab but not docetaxel, after disease progression suggests a delayed anticancer effect with the immunotherapy.  
 
2019 Update
A literature search conducted through December 2018 did not reveal any new information that would prompt a change in the coverage statement.
 
2019 Update
 
Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)–programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy (Horn, L, Mansfield, A, Szczesna, A, et. al., 2018).
A double-blind, placebo-controlled, phase 3 trial was conducted to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat population (Horn, L, Mansfield, A, Szczesna, A, et. al., 2018).
patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P=0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P=0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed (Horn, L, Mansfield, A, Szczesna, A, et. al., 2018).
The addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone (Horn, L, Mansfield, A, Szczesna, A, et. al., 2018).
 
The treatment of several solid and hematologic malignancies with immune checkpoint inhibitors has dramatically changed the cancer treatment paradigm. However, no checkpoint inhibitors were previously approved for the treatment of triple-negative breast cancer (TNBC), a difficult-to-treat disease with a high unmet therapeutic need. Based on IMpassion130 clinical trial (NCT02425891), the Food and Drug Administration (FDA) has recently granted an accelerated approval for atezolizumab (TECENTRIQ®), a monoclonal antibody drug targeting PD-L1, plus chemotherapy (Abraxane; nab®-Paclitaxel) for the treatment of adults with PD-L1-positive, unresectable, locally advanced or metastatic TNBC. The FDA has also approved the Ventana diagnostic antibody SP142 as a companion test for selecting TNBC patients for treatment with atezolizumab (Cyprian, F. S., Akhtar, S., Gatalica, Z., & Vranic, S, 2019).
Although breast cancer has been initially considered a “non-immunogenic” cancer, numerous studies have now shown PD-L1 expression in both cancer and inflammatory cells (tumor infiltrating lymphocytes [TILs]). PD-L1 positivity in cancer or inflammatory cells has been reported across the breast cancer histotypes [12-26]. In particular, ER-negative breast cancers (TNBC and HER2 positive) have been shown to be “immunogenic” and potentially amenable for the trials (Cyprian, F. S., Akhtar, S., Gatalica, Z., & Vranic, S, 2019).
 
The most remarkable results have been recently achieved in the clinical trial IMpassion130 (NCT02425891) [44]. This study led the Food and Drug Administration (FDA) to grant accelerated approval for atezolizumab (TECENTRIQ), anti-PD-L1 agent) in combination with chemotherapy using a solvent-free, nanoparticle albumin-bound (nab) formulation of paclitaxel (nab)-Paclitaxel; Abraxane) for the treatment of patients with TNBC (date of approval: March 8, 2019) (Cyprian, F. S., Akhtar, S., Gatalica, Z., & Vranic, S, 2019).
The approval was based on the randomized trial involving 902 TNBC patients with unresectable, locally advanced, and/or
metastatic TNBC without prior treatment for the metastatic disease. Patients were randomized (1:1) to receive ezolizumab
plus, chemotherapy with Abraxanevs. placebo plus Abraxane. The possible rationale for combining the checkpoint inhibitor with taxane-based chemotherapy that inhibits mitosis was that it may enhance tumor-antigen release and antitumor responses to immune checkpoint inhibition (Cyprian, F. S., Akhtar, S., Gatalica, Z., & Vranic, S, 2019).
 
One of the important findings in the IMpassion130 trial is the efficiency of combined therapy (immunotherapy + conven-
tional chemotherapy). This recent FDA approval of atezolizumab plus chemo-therapy for the treatment of adults with PD-L1-positive, unresectable, locally advanced, or metastatic TNBC represents the first cancer immunotherapy regimen to be approved for the management of breast cancer. It is truly a landmark therapeutic development for patients with TNBC given the limited treatment options available for this heterogeneous, but a highly aggressive subtype of breast cancer
Chemotherapy alone had been the mainstay of treatment for many years for TNBC and so the approval of this checkpoint inhibitor combination for people with PD-L1-positive TNBC disease fulfills an unmet medical need (Cyprian, F. S., Akhtar, S., Gatalica, Z., & Vranic, S, 2019).

CPT/HCPCS:
C9483Injection, atezolizumab, 10 mg
J3490Unclassified drugs
J3590Unclassified biologics
J9022Injection, atezolizumab, 10 mg

References: Cyprian, F. S., Akhtar, S., Gatalica, Z., & Vranic, S.(2019) Targeted immunotherapy with a checkpoint inhibitor in combination with chemotherapy: A new clinical paradigm in the treatment of triple-negative breast cancer. Bosnian Journal of Basic Medical Sciences. https://doi.org/10.17305/bjbms.2019.4204

Fehrenbacher et al; POPLAR Study Group.(2016) Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. doi: 10.1016/S0140-6736(16)00587-0. Epub 2016 Mar 10.

Fehrenbacher L., Spira A., Ballinger M., et al.,(2016) Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. doi: 10.1016/S0140-6736(16)00587-0. Epub 2016 Mar 10.

Horn, L., Mansfield, A., Szczensna, A., Havel, L., et. al.(2018) First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 2018; 379:2220-2229. DOI: 10.1.1056/NEJMoa1809064

Rittmeyer et al; OAK Study Group.(2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. doi: 10.1016/S0140-6736(16)32517-X. Epub 2016 Dec 13.

Rosenberg JE., Hoffman-Censits J., Powles T., et al.(2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet.2016 May 7;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4. Epub 2016 Mar 4.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.