| Coverage Policy Manual | |
| Policy #: | 2016016 |
| Category: | Pharmacy |
| Initiated: | July 2016 |
| Last Review: | January 2025 |
|
|
|
|||||||||||
| 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).
On September 12, 2024, the Food and Drug Administration approved atezolizumab with hyaluronidase (Tecentriq Hybreza) new subcutaneous formulation of the drug.
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 March 12, 2025
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
ATEZOLIZUMAB (e.g., Tecentriq)
Atezolizumab (e.g., Tecentriq) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health for the following indications:
For FDA labeled indications, Atezolizumab (e.g., Tecentriq) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication in the dosage and administration section.
FDA Labeled Indications:
The use of this drug is covered if an FDA-approved oncologic indication exists [not listed as an indication below with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”)].
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
Off-label Indications:
The use of this drug for off-label indications not listed below is subject to policy 2000030.
The following indications are covered when the individual meets the related NCCN category 1 or 2A recommendations specific to the indications below (e.g., histology, cancer staging, surgical status, mono- or combination therapy, and previous lines of therapy):
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications.
Dosage and Administration
Dosing per FDA Guidelines unless otherwise specified below.
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 (e.g., Tecentriq) is:
NSCLC
SCLC
HCC
Melanoma
ASPS
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 (e.g., Tecentriq), 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 (e.g., Tecentriq), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
ATEZOLIZUMAB WITH HYALURONIDASE (e.g., Tecentriq Hybreza)
Atezolizumab with Hyaluronidase (e.g., Tecentriq Hybreza) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health for the following indications:
For FDA labeled indications, Atezolizumab with Hyaluronidase (e.g., Tecentriq Hybreza) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication in the dosage and administration section.
FDA Labeled Indications:
The use of this drug is covered if an FDA-approved oncologic indication exists [not listed as an indication below with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”)].
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
Off-label Indications:
The use of this drug for off-label indications not listed below is subject to policy 2000030.
The following indications are covered when the individual meets the related NCCN category 1 or 2A recommendations specific to the indications below (e.g., histology, cancer staging, surgical status, mono- or combination therapy, and previous lines of therapy):
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications.
Dosage and Administration
Dosing per FDA Guidelines unless otherwise specified below.
Administer Atezolizumab with Hyaluronidase subcutaneously.
The recommended dose of Atezolizumab with Hyaluronidase (e.g., Tecentriq Hybreza) is 1,875 mg atezolizumab and 30,000 units hyaluronidase subcutaneously every 3 weeks until disease recurrence or unacceptable toxicity.
Atezolizumab with Hyaluronidase is available as 1,875mg-30,000units/15mL Solution for Subcutaneous Injection.
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 with Hyaluronidase (e.g., Tecentriq Hybreza, 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 with Hyaluronidase (e.g., Tecentriq Hybreza, 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 15, 2025 to March 11, 2025
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:
FDA Labeled Indications:
For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
Off-label Indications:
For off-label indications, authorizations will not exceed 1680 mg for adult individuals or 1200 mg for pediatric individuals aged 2 years and older unless medical literature supports a higher dose.
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
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).
Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications.
Dosage and Administration
Dosing per FDA Guidelines where applicable. For off-label indications, authorizations will not exceed 1680 mg for adult individuals or 1200 mg for pediatric individuals aged 2 years and older unless medical literature supports a higher dose.
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 (e.g., Tecentriq) is:
NSCLC
SCLC
HCC
Melanoma
ASPS
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 (e.g., Tecentriq), 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 (e.g., Tecentriq), 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 10, 2024 through January 14, 2025
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:
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
NSCLC
Small Cell Lung Cancer
Hepatocellular Carcinoma
Melanoma
ASPS
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:
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
NSCLC
Small Cell Lung Cancer
Hepatocellular Carcinoma
Melanoma
ASPS
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:
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:
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.
3. Small Cell Lung Cancer (SCLC)
4. Hepatocellular Carcinoma (HCC)
5. Melanoma
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
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:
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 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:
2. Non-Small Cell Lung Cancer (NSCLC)
3. Triple-Negative Breast Cancer (TNBC)
4. Small Cell Lung Cancer (SCLC)
5. Hepatocellular Carcinoma (HCC)
6. Melanoma
Off Label
Dosage and administration:
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:
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
“Due to the length of the policy criteria for dates of service prior to January 1, 2021 is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com”
|
|
|
|
| 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)
2025 Update
IMbrave150 demonstrated that atezolizumab plus bevacizumab led to significantly improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib in patients with unresectable hepatocellular carcinoma at the primary analysis (after a median 8.6 months of follow-up). Updated data after 12 months of additional follow-up presented.
Patients with systemic treatment-naive, unresectable hepatocellular carcinoma were randomized 2:1 to receive 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily in this open-label, phase III study. Co-primary endpoints were OS and PFS by independently assessed RECIST 1.1 in the intention-to-treat population. Secondary efficacy endpoints included objective response rates and exploratory subgroup efficacy analyses. This is a post hoc updated analysis of efficacy and safety.
From March 15, 2018, to January 30, 2019, 501 patients (intention-to-treat population) were randomly allocated to receive atezolizumab plus bevacizumab (n = 336) or sorafenib (n = 165). On August 31, 2020, after a median 15.6 (range, 0-28.6) months of follow-up, the median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab plus bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR] 0.66; 95% CI 0.52-0.85; descriptive p <0.001). The median PFS was 6.9 (95% CI 5.7-8.6) and 4.3 (95% CI 4.0-5.6) months in the respective treatment groups (HR 0.65; 95% CI 0.53-0.81; descriptive p < 0.001). Treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 and 72 (46%) of 156 safety-evaluable patients in the respective groups, and treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients.
After longer follow-up, atezolizumab plus bevacizumab maintained clinically meaningful survival benefits over sorafenib and had a safety profile consistent with the primary analysis. (Cheng, 2022)
March 2025 Update
IMscin001 (NCT03735121) was an open-label, multi-center, international, randomized study conducted in adult individuals with locally advanced or metastatic NSCLC who were not exposed to cancer immunotherapy and who have disease progression following platinum-based chemotherapy. Individuals were excluded if they had a history of autoimmune disease; active or corticosteroid-dependent brain metastases; received a live, attenuated vaccine within 4 weeks prior to randomization; or received systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive drugs within 2 weeks prior to randomization. A total of 371 individuals were randomized 2:1 to receive either ATEZOLIZUMAB WITH HYALURONIDASE (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously in the thigh every 3 weeks (n = 247) or intravenous atezolizumab 1,200 mg every 3 weeks (n = 124) until disease progression or unacceptable toxicity. The primary outcome measure was atezolizumab exposure (Ctrough and AUC0-21days) of subcutaneous ATEZOLIZUMAB WITH HYALURONIDASE as compared to intravenous atezolizumab [see Clinical Pharmacology (12.3)]. Additional descriptive efficacy outcome measures were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The median age was 64 years (range: 27 to 85); 69% were male; 67% were White, 22% were Asian, and 0.8% were Black or African American; 74% were non-Hispanic or Latino; 26% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 74% had an ECOG PS of 1; and 70% of individuals were current or previous smokers. Sixty-five percent of individuals had non-squamous histology, 5% had known EGFR mutations, 1.6% had known ALK rearrangements, 36% had known PD-L1 positive tumors, 16% had asymptomatic CNS metastases at baseline. Eighty percent of individuals had received only one prior therapeutic regimen for NSCLC. At the primary analysis, the confirmed ORR was 9% (95% CI: 5, 13) in the subcutaneous ATEZOLIZUMAB WITH HYALURONIDASE arm and 8% (95% CI: 4, 14) in the intravenous atezolizumab arm. After further follow up, no notable differences in PFS and OS were observed between individuals who received subcutaneous ATEZOLIZUMAB WITH HYALURONIDASE and individuals who received intravenous atezolizumab.
|
|
|
|
| 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 Gutzmer R, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Manikhas GM, Yan Y, Huang KC, Uyei A, McNally V, McArthur GA, Ascierto PA.(2020) Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Jun 13;395(10240):1835-1844. doi: 10.1016/S0140-6736(20)30934-X. Erratum in: Lancet. 2020 Aug 15;396(10249):466. PMID: 32534646. Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroglu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR.(2020) Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med. 2020 Oct 1;383(14):1328-1339. doi: 10.1056/NEJMoa1917346. PMID: 32997907. 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 NCCN Drugs & Biologics Compendium® for Atezolizumab, (e.g., Tecentriq®), © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed [January 4, 2024]. To view the most recent and complete version of the Compendium, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Nishio M, Barlesi F, West H, Ball S, Bordoni R, Cobo M, Longeras PD, Goldschmidt J Jr, Novello S, Orlandi F, Sanborn RE, Szalai Z, Ursol G, Mendus D, Wang L, Wen X, McCleland M, Hoang T, Phan S, Socinski MA.(2021) Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial. J Thorac Oncol. 2021 Apr;16(4):653-664. doi: 10.1016/j.jtho.2020.11.025. Epub 2020 Dec 14. PMID: 33333328. 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. Roche.(2020) Roche’s Tecentriq improves overall survival as a first-line monotherapy in certain people with advanced non-small cell lung cancer [news release]. https://www.roche.com/media/releases/med-cor-2019-09-27b.htm. Accessed June 8, 2020 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. U.S. Food and Drug Administration (FDA).(2023) Tecentriq. Prescribing Information. https:// https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761034s047lbl.pdf. Last accessed January 10, 2023. West H, McCleod M, Hussein M, et. al.(2019) Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer Lancet Oncol. 2019 Jul; 20(7):924-937. doi: 10.1016/S1470-2045(19)30167-6. Epub 2019 May 20. |
|
|
|
|
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 © 2025 American Medical Association. |
|