Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2016016
Category:	Pharmacy
Initiated:	July 2016
Last Review:	January 2024

Atezolizumab (e.g., Tecentriq®)

Description:

Atezolizumab 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. Atezolizumab is marketed by Genentech based in San Francisco, California. The Ventana PD-L1 (SP142) assay complementary diagnostic for Atezolizumab is marketed by Ventana Medical Systems, based in Tucson, Arizona.

Atezolizumab is reserved for the treatment of individuals 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.

Regulatory Status

On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab (e.g., 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 (e.g., Tecentriq) was approved for the treatment of metastatic NSCLC in individuals 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 individuals with extensive-stage small cell lung cancer.

On December 3, 2019, the U.S. Food and Drug Administration approved atezolizumab in combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult individuals with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations.

On May 18, 2020, the FDA approved Genentech’s atezolizumab (e.g., Tecentriq) as a first-line treatment for adults with metastatic non-small cell lung cancer (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.

On May 29, 2020, the FDA approved atezolizumab (e.g., Tecentriq) in combination with bevacizumab, for the treatment of individuals with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

On July 30, 2020, the Food and Drug Administration approved Atezolizumab (e.g., Tecentriq) in combination with cobimetinib (e.g., Cotellic) and vemurafenib (e.g., Zelboraf) for the treatment of individuals with unresectable or metastatic BRAF V600 mutation positive melanoma.

On April 13, 2021, the Food and Drug Administration removed the approval of atezolizumab (e.g., Tecentriq) for the treatment of adult individuals with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy.

On October 6, 2021, the Food and Drug Administration removed the approval, previously approved under accelerated approval, atezolizumab (e.g., Tecentriq) for the treatment of adult individuals with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering > 1% of the tumor area), as determined by an FDA-approved test.

On November 29, 2022 announced that it would be voluntarily withdrawing the indication of atezolizumab (e.g. Tecentriq) for the treatment of adults with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express programmed death-ligand 1 (PD-L1–stained tumor-infiltrating immune cells covering ≥5% of the tumor area) or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

On December 9, 2022, the Food and Drug Administration approved a new indication for atezolizumab (e.g., Tecentriq) as a single agent for the treatment of adult and pediatric individuals 2 years of age and older with unresectable or metastatic alveolar soft part sarcoma (ASPS).

Coding

See CPT/HCPCS Code section below.

Policy/
Coverage:

Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.

Effective January 10, 2024

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 in improving health for the following indications:

1. Urothelial Carcinoma

a. Used as a single agent for recurrent or metastatic disease as first-line systemic therapy in the following:

i. Cisplatin ineligible individuals whose tumors express PD-L1 (NCCN 2A) OR

ii. Individuals who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression. (NCCN 2A); AND

iii. Will not be used:

1. As first line therapy for urothelial carcinoma at any stage; OR

2. As treatment of renal cell carcinoma at any stage.

2. Non-Small Cell Lung Cancer (NSCLC)

a. The treatment of individuals with metastatic non-small cell lung cancer:

i. For the first-line treatment of the following:

1. Adult individuals 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. (NCCN 1) OR

2. Adult individuals with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations in combination with bevacizumab, paclitaxel, and carboplatin. (NCCN 1); OR

3. Adult individuals with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations, in combination with paclitaxel protein-bound and carboplatin; OR (NCCN 2A); OR

4. Adult individuals with Stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test, and are negative for EGFR exon 19 deletion or exon 21 L858R mutations or ALK rearrangements [when used as adjuvant therapy following resection and platinum-based chemotherapy (NCCN 2A)]. OR

ii. For the second-line or subsequent treatment of :

1. Adult individuals with metastatic NSCLC who have disease progression during or following first-line chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving atezolizumab. (NCCN 1); AND

b. Will not be used as first line therapy for NSCLC at any stage, except in adult individuals with advanced or metastatis NSCLC.

3. Small Cell Lung Cancer (SCLC)

a. In combination with carboplatin and etoposide, followed by single agent maintenance for extensive stage disease in individuals (NCCN 1 and 2A):

i. Without localized symptomatic sites or brain metastases and good performance status (PS 0-2); OR

ii. Without localized symptomatic sites or brain metastases and poor PS (3-4) due to SCLC; OR

iii. With localized symtomatic sites [used with radiation therapy (typically seuential) if spinal cord compression]; OR

iv. With brain metastases.

4. Hepatocellular Carcinoma (HCC)

a. Preferred first-line treatment in combination with bevacizumab for individuals (Child-Pugh Class A only) who (NCCN 1):

i. Have unresectable disease and are not a transplant candidate

ii. Have liver-confined disease, inoperable by performance status, comorbidity or with minimal or uncertain extrahepatic disease

iii. Have metastatic disease or extensive liver tumor burden

5. Melanoma

a. Useful in certain circumstances in combination with vemurafenib and cobimetnib as:

i. Second-line or subsequent therapy option for metastatic or unresectable disease with a BRAF V600 activating mutation following progression or intolerance if BRAF/MEK and/or PD(L)-1 checkpoint inhibition not previously used (NCCN 2A), OR

ii. May be considered as re-induction therapy if prior combination BRAF/MEK + PD(L)-1 checkpoint inhibition resulted in disease control (complete response, partial response, or stable disease), no residual toxicity, and disease progression/relapse greater than 3 months after treatment discontinuation. (NCCN 2A)

6. Alveolar Soft Part Sarcoma (ASPS)

a. For the treatment of adult and pediatric individuals 2 years of age and older with unresectable or metastatic ASPS. (FDA, 2023)

7. Cervical Cancer

a. First-line, second-line or subsequent therapy as clinically appropriate (if not used previously as first-line) for persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC) in one of the following:

i. In combination with cisplatin and etoposide (NCCN 2A), OR

ii. In combination with carboplatin and etoposide (NCCN 2A)

8. Mesothelioma: Peritoneal

a. Subsequent systemic therapy for ECOG performance status (PS) 0-2 in combination with bevacizumab if not previously treated with immune checkpoint inhibitors (NCCN 2A)

The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).

Dosage and Administration

Dosing per FDA Guidelines

Administer Atezolizumab intravenously over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

The recommended dose of Atezolizumab is:

Urothelial Cancer

1200 mg intravenously over 60 minutes every 3 weeks until disease progression or unacceptable toxicity. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

NSCLC

In the adjuvant setting, administer TECENTRIQ following resection and up to 4 cycles of platinum-based chemotherapy as 840 mg every 2 weeks, 1200 mg every 3 weeks or 1680 mg every 4 weeks for up to 1 year.
In the metastatic setting, administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.
When administering with chemotherapy with or without bevacizumab, administer TECENTRIQ prior to chemotherapy and bevacizumab when given on the same day.

Small Cell Lung Cancer

Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. When administering with carboplatin and etoposide, administer TECENTRIQ prior to chemotherapy when given on the same day.

Hepatocellular Carcinoma

Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. Administer TECENTRIQ prior to bevacizumab when given on the same day. Bevacizumab is administered at 15 mg/kg every 3 weeks.

Melanoma

Following completion of a 28 day cycle of cobimetinib and vemurafenib, administer TECENTRIQ 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks with cobimetinib 60 mg orally once daily (21 days on /7 days off) and vemurafenib 720 mg orally twice daily.

ASPS

Adults: Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.
Pediatric individuals 2 years of age and older: 15 mg/kg (up to a maximum of 1200 mg), every 3 weeks

Atezolizumab is available as an injection: 840 mg/14 mL (60 mg/mL) and 1200 mg/20 mL (60 mg/mL) solution in a single-dose vial.

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, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcome.

For members with contracts without primary coverage criteria, atezolizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective January 25, 2023 To January 9, 2024

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:

Urothelial Carcinoma

Used as a single agent for recurrent or metastatic disease as first-line systemic therapy in the following:

a. Cistplatin ineligible individuals whose tumors expresss PD-L1 (NCCN 2A) OR

b. Individuals who are not eligible for any plantinum-containing chemotherapy regadless of PD-L1 expression. (NCCN 2A)

2. Non-Small Cell Lung Cancer (NSCLC)

The treatment of individuals with metastatic non-small cell lung cancer:

a. For the first-line treatment of the following:

Adult individuals 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. (NCCN 1) OR
Adult individuals with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations in combination with bevacizumab, paclitaxel, and carboplatin. (NCCN 1)
Adult individuals with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations, in combination with paclitaxel protein-bound and carboplatin; OR (NCCN 2A); OR
Adult individuals with Stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test, and are negative for EGFR exon 19 deletion or exon 21 L858R mutations or ALK rearrangements [when used as adjuvant therapy following resection and platinum-based chemotherapy (NCCN 2A)]. OR

b. For the second-line or subsequent treatment of :

Adult individuals with metastatic NSCLC who have disease progression during or following first-line chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving atezolizumab. (NCCN 1)

3. Small Cell Lung Cancer (SCLC)

a. In combination with carboplatin and etoposide, for the first-line treatment of adult individuals with extensive-stage small cell lung cancer (ES-SCLC). (NCCN 2A)

4. Hepatocellular Carcinoma (HCC)

Preferred first-line treatment in combination with bevacizumab for individuals (Child-Pugh Class A only) who (NCCN 1):

a. Have unresectable disease and are not a transplant candidate

b. Have liver-confined disease, inoperable by performance status, comorbidity or with minimal or uncertain extrahepatic disease

c. Have metastatic disease or extensive liver tumor burden

5. Melanoma

b. Useful in certain circumstances in combination with vemurafenib and cobmetnib as:

Second-line or subsequent therapy option for metastatic or unresectable disease with a BRAF V600 activating mutation following progression or intolerance if BRAF/MEK and/or PD(L)-1 checkpoint inhibition not previously used (NCCN 2A), OR
May be considered as re-induction therapy if prior combination BRAF/MEK + PD(L)-1 checkpoint inhibition resulted in disease control (complete response, partial response, or stable disease), no residual toxicity, and disease progression/relapse greater than 3 months after treatment discontinuation. (NCCN 2A)

6. Alveolar Soft Part Sarcoma (ASPS)

For the treatment of adult and pediatric individuals 2 years of age and older with unresectable or metastatic ASPS. (FDA, 2023)

7. Cervical Cancer

First-line, second-line or subsequent therapy as clinically appropriate (if not used previously as first-line) for persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC) in one of the following:

a. In combination with cisplatin and etoposide (NCCN 2A), OR

b. In combination with carboplatin and etoposide (NCCN 2A)

8. Mesothelioma: Peritoneal

Subsequent systemic therapy for ECOG performance status (PS) 0-2 in combination with bevacizumab if not previously treated with immune checkpoint inhibitors (NCCN 2A)

Dosage and Administration

Dosing per FDA Guidelines

Administer Atezolizumab intravenously over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

The recommended dose of Atezolizumab is:

Urothelial Cancer

1200 mg intravenously over 60 minutes every 3 weeks until disease progression or unacceptable toxicity. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

NSCLC

• In the adjuvant setting, administer TECENTRIQ following resection and up to 4 cycles of platinum-based chemotherapy as 840 mg every 2 weeks, 1200 mg every 3 weeks or 1680 mg every 4 weeks for up to 1 year.

• In the metastatic setting, administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.

• When administering with chemotherapy with or without bevacizumab, administer TECENTRIQ prior to chemotherapy and bevacizumab when given on the same day.

Small Cell Lung Cancer

• Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. When administering with carboplatin and etoposide, administer TECENTRIQ prior to chemotherapy when given on the same day.

Hepatocellular Carcinoma

• Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. Administer TECENTRIQ prior to bevacizumab when given on the same day. Bevacizumab is administered at 15 mg/kg every 3 weeks.

Melanoma

• Following completion of a 28 day cycle of cobimetinib and vemurafenib, administer TECENTRIQ 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks with cobimetinib 60 mg orally once daily (21 days on /7 days off) and vemurafenib 720 mg orally twice daily.

ASPS

• Adults: Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.

• Pediatric patients individuals 2 years of age and older: 15 mg/kg (up to a maximum of 1200 mg), every 3 weeks

Atezolizumab is available as an injection: 840 mg/14 mL (60 mg/mL) and 1200 mg/20 mL (60 mg/mL) solution in a single-dose vial.

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 individuals with advanced or metastatic NSCLC.

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 November 1, 2021 to January 24, 2023

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 (NCCN 2A), 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) (NCCN 2A) OR
who are not eligible for any platinum containing chemotherapy regardless of PD-L1 status (NCCN 2A)

2. Non-Small Cell Lung Cancer (NSCLC)

The treatment of patients with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy.

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. (NCCN 1)
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. (NCCN 1)
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 atezolizumab. (NCCN 1)
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. (NCCN 2A)

3. 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). (NCCN 1)

4. Hepatocellular Carcinoma (HCC)

In combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy. (NCCN 1)

5. Melanoma

In combination with cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. (NCCN 2A)

Dosage and Administration

Per FDA label guidelines.

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

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).

Effective January 2021 to October 31, 2021

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 (NSCLC)

The treatment of patients with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy.

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.
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.
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.

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).

5. Hepatocellular Carcinoma (HCC)

In combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy.

6. Melanoma

In combination with cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Off Label

NCCN 1, 2A, and 2B Recommendations in accordance with Coverage Policy #2000030.

Dosage and administration:

Per FDA label guidelines.

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

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).

Effective June 2020 to December 2020

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 (NSCLC)

The treatment of patients with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy.

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.
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.
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.

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).

5. Hepatocellular Carcinoma (HCC)

In combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy

Off Label

NCCN 1, 2A, and 2B Recommendations in accordance with Coverage Policy #2000030.

Dosage and administration:

Per FDA label guidelines.

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

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 January 2020 to May 2020

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 (NSCLC)

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.
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.

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:

Per FDA label guidelines.

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

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

Effective April 2019 to December 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:

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

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

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:

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

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

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

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:

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

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

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

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:

Disease progression during or following platinum-containing chemotherapy, OR
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:

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, 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:

Disease progression during or following platinum-containing chemotherapy, OR
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:

First line therapy for urothelial carcinoma at any stage
Treatment of renal cell carcinoma at any stage
Treatment of non-small cell lung cancer at any stage
Treatment of melanoma at any stage

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).

January 2020 Update

The efficacy of TECENTRIQ with paclitaxel protein-bound and carboplatin was evaluated in IMpower130 (NCT02367781), a multicenter, randomized (2:1), open-label trial in patients with stage IV non-squamous NSCLC. Patients with Stage IV non-squamous NSCLC who had received no prior chemotherapy for metastatic disease, but could have received prior EGFR or ALK kinase inhibitor, if appropriate, were eligible. The trial excluded patients with history of autoimmune disease, administration of live attenuated vaccine within 28 days prior to randomization, administration of immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to randomization, and active or untreated CNS metastases.

Between April 16, 2015, and Feb 13, 2017, 724 patients were randomly assigned and 723 were included in the intention-to-treat population (one patient died before randomisation, but was assigned to a treatment group; this patient was excluded from the intention-to-treat population) of the atezolizumab plus chemotherapy group (483 patients in the intention-to-treat population and 451 patients in the intention-to-treat wild-type population) or the chemotherapy group (240 patients in the intention-to-treat population and 228 patients in the intention-to-treat wild-type population). Median follow-up in the intention-to-treat wild-type population was similar between groups (18·5 months [IQR 15·2-23·6] in the atezolizumab plus chemotherapy group and 19·2 months [15·4-23·0] in the chemotherapy group). In the intention-to-treat wild-type population, there were significant improvements in median overall survival (18·6 months [95% CI 16·0-21·2] in the atezolizumab plus chemotherapy group and 13·9 months [12·0-18·7] in the chemotherapy group; stratified hazard ratio [HR] 0·79 [95% CI 0·64-0·98]; p=0·033) and median progression-free survival (7·0 months [95% CI 6·2-7·3] in the atezolizumab plus chemotherapy group and 5·5 months [4·4-5·9] in the chemotherapy group; stratified HR 0·64 [95% CI 0·54-0·77]; p<0·0001]). The most common grade 3 or worse treatment-related adverse events were neutropenia (152 [32%] of 473 in the atezolizumab plus chemotherapy group vs 65 [28%] of 232 in the chemotherapy group), anaemia (138 [29%] vs 47 [20%]), and decreased neutrophil count (57 [12%] vs 19 [8%]). Treatment-related serious adverse events were reported in 112 (24%) of 473 patients in the atezolizumab plus chemotherapy group and 30 (13%) of 232 patients in the chemotherapy group. Treatment-related (any treatment) deaths occurred in eight (2%) of 473 patients in the atezolizumab plus chemotherapy group and one (<1%) of 232 patients in the chemotherapy group.

IMpower130 showed a significant and clinically meaningful improvement in overall survival and a significant improvement in progression-free survival with atezolizumab plus chemotherapy versus chemotherapy as first-line treatment of patients with stage IV non-squamous non-small-cell lung cancer and no ALK or EGFR mutations. No new safety signals were identified. The study supports the benefit of atezolizumab, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer. (West H, McCleod M, Hussein M, et. al., 2019)

June 2020 Update

A Phase 3 IMpower110 study showed an improvement in overall survival of 7.1 months in patients receiving Tecentriq monotherapy, compared with chemotherapy in people with high PD-L1 expression. No new safety signals were identified from Tecentriq’s safety profile characterized in previous approvals for other cancers. Treatment-related adverse events were reported in 12.9% of people receiving Tecentriq compared with 44.1% of people receiving chemotherapy. (Roche, 2020)

In a global, open-label, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progression-free survival in the intention-to-treat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

The intention-to-treat population included 336 patients in the atezolizumab-bevacizumab group and 165 patients in the sorafenib group. At the time of the primary analysis (August 29, 2019), the hazard ratio for death with atezolizumab-bevacizumab as compared with sorafenib was 0.58 (95% confidence interval [CI], 0.42 to 0.79; P<0.001). Overall survival at 12 months was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab-bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Median progression-free survival was 6.8 months (95% CI, 5.7 to 8.3) and 4.3 months (95% CI, 4.0 to 5.6) in the respective groups (hazard ratio for disease progression or death, 0.59; 95% CI, 0.47 to 0.76; P<0.001). Grade 3 or 4 adverse events occurred in 56.5% of 329 patients who received at least one dose of atezolizumab-bevacizumab and in 55.1% of 156 patients who received at least one dose of sorafenib. Grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab-bevacizumab group; however, other high-grade toxic effects were infrequent.

In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib.

2021 Update

In a randomized, double blind, placebo-controlled phase 3 study, IMspire150 , conducted at 112 institutes in 20 countries, patients with unresectable stage IIIc-IV, BRAFV600 mutation-positive melanoma were randomly assigned 1:1 to 28-day cycles of atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) or atezolizumab placebo, vemurafenib, and cobimetinib (control group). In cycle 1, all patients received vemurafenib and cobimetinib only; atezolizumab placebo was added from cycle 2 onward. Randomization was stratified by lactate dehydrogenase concentration and geographical region. Blinding for atezolizumab was achieved by means of an identical intravenous placebo, and blinding for vemurafenib was achieved by means of a placebo tablet. The primary outcome was investigator-assessed progression-free survival.

Between Jan 13, 2017, and April 26, 2018, 777 patients were screened and 514 were enrolled and randomly assigned to the atezolizumab group (n=256) or control group (n=258). At a median follow-up of 18·9 months (IQR 10·4-23·8), progression-free survival as assessed by the study investigator was significantly prolonged with atezolizumab versus control (15·1 vs 10·6 months; hazard ratio [HR] 0·78; 95% CI 0·63-0·97; p=0·025). Common treatment-related adverse events (>30%) in the atezolizumab and control groups were blood creatinine phosphokinase increased (51·3% vs 44·8%), diarrhea (42·2% vs 46·6%), rash (40·9%, both groups), arthralgia (39·1% vs 28·1%), pyrexia (38·7% vs 26·0%), alanine aminotransferase increased (33·9% vs 22·8%), and lipase increased (32·2% vs 27·4%); 13% of patients in the atezolizumab group and 16% in the control group stopped all treatment because of adverse events.

The addition of atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAFV600 mutation-positive advanced melanoma. (ClinicalTrials.gov, NCT02908672) (Gutzmer R, Stroyakovskiy D, Gogas H, et. al., 2020)

2022 Update

Chemotherapy-naive patients with stage IV nonsquamous NSCLC without sensitizing EGFR or ALK genetic alterations were randomized in a one-to-one ratio to receive four or six cycles of carboplatin or cisplatin plus pemetrexed (PP) or APP every 3 weeks, followed by maintenance therapy with atezolizumab plus pemetrexed or pemetrexed alone. Co-primary end points were overall survival (OS) and investigator-assessed progression-free survival (PFS).

The intention-to-treat population included 578 patients (APP, n = 292; PP, n = 286). At the primary PFS analysis (May 22, 2018; median follow-up, 14.8 mo), APP exhibited significant PFS improvement versus PP (median = 7.6 versus 5.2 mo, stratified hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.49-0.72, p < 0.0001). OS for the APP group was numerically better but not statistically significant at the interim (May 22, 2018; median = 18.1 versus 13.6 mo, stratified HR = 0.81, 95% CI: 0.64-1.03, p = 0.0797) and final analyses (July 18, 2019; median = 17.5 versus 13.6 mo; stratified HR = 0.86, 95% CI: 0.71-1.06, p = 0.1546). The OS and PFS results favored APP versus PP across subgroups. Grade 3 or 4 treatment-related adverse events occurred in 54.6% (APP) and 40.1% (PP) of patients; grade 5 treatment-related events occurred in 3.8% and 2.9%, respectively.

IMpower132 met its co-primary PFS end point but not its co-primary OS end point, with numerical improvement for OS in the APP arm. APP had a manageable safety profile, with no new or unexpected safety signals identified. (Nishio M, Barlesi F, West H, et.al., 2021)

January 2023 Update

The efficacy of TECENTRIQ was evaluated in study ML39345 (NCT03141684), an open-label, single-arm study, in 49 adult and pediatric patients aged 2 years and older with unresectable or metastatic ASPS. Eligible patients were required to have histologically or cytologically confirmed ASPS that was not curable by surgery, and an ECOG performance status of ≤ 2.

Patients were excluded if they had known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, known clinically significant liver disease, or history of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.

Adult patients received 1200 mg intravenously and pediatric patients received 15 mg/kg (up to a maximum of 1200 mg) intravenously once every 21 days until disease progression or unacceptable toxicity.

The major efficacy outcomes were Overall Response Rate (ORR) and Duration of Response (DOR) by Independent Review Committee according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

A total of 49 patients were enrolled. The median age of patients was 31 years (range: 12-70); 2% of adult patients (n=47) were ≥65 years of age and the pediatric patients (n=2) were ≥12 years of age; 51% of patients were female, 55% White, 29% Black or African American, 10% Asian; 53% had an ECOG performance status of 0 and 45% had an ECOG performance status of 1. All patients had prior surgery for ASPS and 55% received at least one prior line of treatment for ASPS; 55% received radiotherapy and 53% received chemotherapy. Of the patients who reported staging at initial diagnosis, all were Stage IV. (FDA, 2023)

2024 Update

A randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay was conducted. Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. Overall survival (primary end point) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with respect to EGFR mutations or ALK translocations. Within the population with EGFR and ALK wild-type tumors, overall survival and progression-free survival were also prospectively assessed in subgroups defined according to findings on two PD-L1 assays as well as by blood-based tumor mutational burden.

Overall, 572 patients were enrolled. In the subgroup of patients with EGFR and ALK wild-type tumors who had the highest expression of PD-L1 (205 patients), the median overall survival was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P = 0.01). Among all the patients who could be evaluated for safety, adverse events occurred in 90.2% of the patients in the atezolizumab group and in 94.7% of those in the chemotherapy group; grade 3 or 4 adverse events occurred in 30.1% and 52.5% of the patients in the respective groups. Overall and progression-free survival favored atezolizumab in the subgroups with a high blood-based tumor mutational burden.

Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type. (Herbst RS, Giaccone G, de Marinis F, et.al., 2020)

CPT/HCPCS:

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.

Finn RS, Qin S, Ikeda M, et al.(2020) Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-1905. doi:10.1056/NEJMoa1915745

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