Atezolizumab (Tecentriq)

General information

Class/mechanism: PD-L1 antibody. Atezolizumab targets PD-L1 (programmed cell death-1 ligand 1) which is expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on T-cells. By interfering with the binding of PD-L1 to T-cell receptors, it can cause upregulation of the anti-tumor immune response.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, Medscape, UpToDate (courtesy of Lexicomp), or the prescribing information.

Toxicity management

• Immunotherapy toxicity management

Diseases for which it is established (work in progress)

• Alveolar soft part sarcoma
• Hepatocellular carcinoma
• Renal cell carcinoma

Diseases for which it is used

• Colorectal cancer, MSI-H or dMMR
• Malignant peritoneal mesothelioma
• Melanoma, BRAF-mutated
• Non-small cell lung cancer
  • Non-small cell lung cancer, nonsquamous
  • Non-small cell lung cancer, squamous
• Small cell lung cancer
• Urothelial carcinoma

Diseases for which it was used

• Breast cancer, triple negative

Patient drug information

• Atezolizumab (Tecentriq) package insert
• Atezolizumab (Tecentriq) patient drug information (Chemocare)
• Atezolizumab (Tecentriq) patient drug information (UpToDate)

History of changes in FDA indication

Alveolar soft part sarcoma

• 2022-12-09: Approved for adult and pediatric patients 2 years of age and older with unresectable or metastatic alveolar soft part sarcoma (ASPS). (Based on Study ML39345)

Breast cancer, triple negative - WITHDRAWN

• 2019-03-08: Granted accelerated approval in combination with paclitaxel protein-bound for adult patients 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 at least 1% of the tumor area) (New disease entity; based on IMpassion130)
  • 2021-10-06: Accelerated approval in combination with paclitaxel protein-bound for adult patients 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 at least 1% of the tumor area) withdrawn. (Based on IMpassion131)

Hepatocellular carcinoma

• 2020-05-29: Approved in combination with bevacizumab for patients with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy. (New disease entity; based on IMbrave150)

Melanoma, BRAF-mutated

• 2020-07-30: Approved in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. (New disease entity; based on IMspire150)

Non-small cell lung cancer

• 2016-10-18: Approval expanded for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab. (New disease entity; based on OAK)
• 2020-05-18: Approved for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (PD-L1 stained at least 50% of tumor cells [TC at least 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering at least 10% of the tumor area [IC at least 10%]), with no EGFR or ALK genomic tumor aberrations. (Approval extended to protein expression-specific monotherapy; non-squamous restriction removed; based on IMpower110)
• 2021-10-15: Approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on at least 1% of tumor cells. (Based on IMpower010)

Non-small cell lung cancer, nonsquamous

• 2018-12-06: Approved in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations. (Approval extended to the first-line setting and restricted to non-squamous histology; based on IMpower150)
• 2019-12-03: Approved in combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult patients with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations. (Approval extended to three-drug combination; based on IMpower130)

Small cell lung cancer

• 2019-03-18: Approved in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). (New disease entity; based on IMpower133)

Urothelial carcinoma - WITHDRAWN

• 2016-05-18: Granted accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy (Based on IMvigor210 previously treated)
  • 2021-04-13: Accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy withdrawn. (Based on IMvigor211)
• 2016-05-18: Granted accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (Based on IMvigor210 previously treated)
  • 2021-04-13: Accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy withdrawn. (Based on IMvigor211)
• 2017-04-17: Granted accelerated approval for an expanded indication for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy, or have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy. (No longer needs to be used after platinum-containing chemotherapy; based on IMvigor210 untreated)
• 2018-06-19: Label revised for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing therapy, and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering at least 5% of the tumor area), as determined by an FDA-approved test. (Conditional approval dependent on PD-L1 expression; based on IMvigor130)
• 2018-06-19: Label revised for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for any platinum-containing therapy regardless of PD-L1 status. (Based on IMvigor130)
• 2022-12-02: All indications for urothelial carcinoma withdrawn at the request of the manufacturer. (Based on IMvigor130)

History of changes in EMA indication

Hepatocellular carcinoma

• 2020-10-27: Extension of indication to include, in combination with with bevacizumab, the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy. (Based on IMbrave150 & GO30140)

Non-small cell lung cancer

• 2017-09-20: Initial marketing authorization as Tecentriq. Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. Patients with EGFR activating mutations or ALK-positive tumour mutations should also have received targeted therapy before receiving Tecentriq. (Based on OAK)
• 2021-04-30: Extension of indication to include the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours express PD-L1. (Based on IMpower110)
• 2022-06-07: Extension of indication to include adjuvant treatment as monotherapy of non-small cell lung cancer (NSCLC) following resection and platinum-based chemotherapy for adult patients whose tumours have PD-L1 expression on at least 50% of tumour cells (TC). (Based on IMpower010)

Non-small cell lung cancer, nonsquamous

• 2019-03-05: Extension of indication to include in combination with bevacizumab, paclitaxel and carboplatin the first-line treatment of adult patients with metastatic nonsquamous non-small cell lung cancer (NSCLC). (Based on IMpower150)
• 2019-09-03: Extension of indication to include Tecentriq, in combination with nab-paclitaxel and carboplatin, for the first-line treatment of adult patients with metastatic non-squamous non-small cell lung cancer (NSCLC) who do not have EGFR mutant or ALK-positive NSCLC.

Small cell lung cancer

• 2019-09-03: Extension of Indication to include, in combination with carboplatin and etoposide, first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

Urothelial carcinoma

• 2017-09-20: Initial marketing authorization as Tecentriq. Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) after prior platinum-containing chemotherapy or who are considered cisplatin ineligible. (Based on IMvigor210 previously treated, IMvigor210 untreated, and IMvigor211)
• 2018-07-02: Indication revised as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) after prior platinum-containing chemotherapy or who are considered cisplatin ineligible and whose tumours have a PD-L1 expression at least 5%. (Based on IMvigor130)

History of changes in Health Canada indication

Hepatocellular carcinoma

• 2020-08-10: New indication, in combination with bevacizumab, for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma who require systemic therapy.

Non-small cell lung cancer

• 2018-04-06: New indication for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (patients with epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase [ALK] tumour aberrations should also have disease progression on a therapy for those aberrations prior to receiving atezolizumab).
• 2021-03-01: New indication as monotherapy for the first-line treatment of patients with metastatic NSCLC whose tumours have high PD-L1 expression (PD-L1 stained at least 50% of tumour cells [TCs] or PD-L1 stained tumour-infiltrating immune cells [ICs] covering at least 10% of the tumour area), as determined by a validated test and who do not have EGFR or ALK genomic tumour aberrations.
• 2022-01-14: New indication as monotherapy, as adjuvant treatment following complete resection and no progression after platinum-based adjuvant chemotherapy for adult patients with Stage II to IIIA NSCLC whose tumours have PD-L1 expression on at least 50% of tumour cells (TCs).

Non-small cell lung cancer, nonsquamous

• 2019-05-24: New indication in combination with bevacizumab, carboplatin, and paclitaxel for the treatment of adult patients with metastatic non-squamous non-small cell lung cancer, with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic non-squamous non-small cell lung cancer.
• 2020-04-02: New indication in combination with carboplatin and nab-paclitaxel for the first-line treatment of adult patients with metastatic non-squamous-non-small cell lung cancer (NSCLC) who do not have EGFR or ALK genomic tumour aberrations.

Small cell lung cancer

• 2019-08-08: New indication in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

Urothelial carcinoma

• 2017-04-12: Initial notice of compliance with conditions to treat patients with locally advanced or metastatic urothelial carcinoma that have received prior platinum based chemotherapy.
  • 2021-03-05: Conditions met

History of changes in PMDA indication

Breast cancer

• 2019-09-20: New indication and a new dosage in an additional dosage form indicated for the treatment of PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or recurrent breast cancer.

Hepatocellular carcinoma

• 2020-09-25: New indication and a new dosage for the treatment of unresectable hepatocellular carcinoma.

Non-small cell lung cancer

• 2018-01-19: New approval for the treatment of unresectable advanced or recurrent non-small cell lung cancer.
• 2022-05-26: New indication and a new dosage for the postoperative adjuvant treatment for PD-L1-positive non-small cell lung cancer.

Small cell lung cancer

• 2019-08-22: New indication and a new dosage for the treatment of extensive-stage small-cell lung cancer.

Also known as

• Code names: MPDL-3280A, RG-7446, RO-5541267
• Brand name: Tecentriq