TECENTRIQ

Atezolizumab is a humanized monoclonal antibody used to prevent the interaction of PD-L1 and PD-1, removing inhibition of immune responses seen in some cancers. 2, 7 This medication is reserved for patients whose tumors express PD-L1, cannot receive platinum-based chemotherapy, or whose tumors do not respond to platinum-based chemotherapy.

Atezolizumab was granted

FDA approval on 18 October 2016.

In November 2022, the manufacturer (Genentech) voluntarily withdrew the use of atezolizumab for the treatment of urothelial carcinoma, previously approved under the FDA's Accelerated Approval Program.

Atezolizumab has approved indications for the following conditions, with the route of administration being intravenous 14 or subcutaneous in combination with Hyaluronidase (human recombinant) 13, in adult patients: Non-Small Cell Lung Cancer (NSCLC) as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage II to IIIA NSCLC whose tumours have PD-L1 expression on ≥ 1% of tumour cells, as determined by an FDA-approved test. for the first-line treatment of adult patients with metastatic NSCLC whose tumours have high PD-L1 expression (PD-L1 stained ≥ 50% of tumour cells or PD-L1 stained tumour-infiltrating immune cells covering ≥ 10% of the tumour area ), as determined by an FDAapproved test, with no EGFR or ALK genomic tumour 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 tumour aberrations. in combination with paclitaxel protein-bound and carboplatin for the firstline 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 tumour aberrations should have disease progression on FDA-approved therapy for NSCLC harbouring these aberrations prior to receiving atezolizumab.

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). in combination with lurbinectedin for the maintenance treatment of adult patients with ES-SCLC whose disease has not progressed after first-line induction therapy with atezolizumab (or atezolizumab/hyaluronidase), carboplatin and etoposide.

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

Melanoma in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Atezolizumab has approved indications for the following condition, administered Intravenous 11, in adult and pediatric patients: Alveolar Soft Part Sarcoma (ASPS) for the treatment of adult and pediatric patients 2 years of age and older with unresectable or metastatic ASPS.

Atezolizumab has an approved indication for the following condition, administered Subcutaneous in combination with Hyaluronidase (human recombinant) 13, in adult patients: for the treatment of adult patients with unresectable or metastatic ASPS.

Atezolizumab is a humanized monoclonal antibody used to prevent the interaction of PD-L1 and PD-1, removing inhibition of immune responses seen in some cancers. 2, 7 This drug has a long duration of action as it is usually given every 3-4 weeks.

Atezolizumab should not be used in patients with immune mediated penumonitis, hepatitis, colitis, and some endocrinopathies.

Pharmacokinetic analysis was performed in patients with metastatic urothelial carcinoma.

In these patients, the AUC was 2.19-2.73day*µg/mL/mg, the C max was 0.27-0.35 µg/mL/mg, and the C min was 0.004-0.008 µg/mL/mg.

The volume of distribution of atezolizumab is 6.91 L. 1, 3.

Monoclonal antibodies are broken down into smaller polypeptides and amino acids.

The half life of atezolizumab is 27 days. 1, 3.

The clearance of atezolizumab is 0.200 L/day. 1, 3.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

Most common adverse reactions (≥ 20% of patients) included: fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation.

Overdose data for atezolizumab is scarce 6 but the most common adverse reactions are fatigue, nausea, cough, dyspnea, decreased appetite, alopecia, constipation, diarrhea, peripheral neuropathies, anemia, headache, neutropenia, and vomiting.

TECENTRIQ intravenously over 60 minutes.

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

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.

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.

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.

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

Pediatric patients 2 years of age and older: 15 mg/kg (up to a maximum of 1200 mg), every 3 weeks 2.1 Patient Selection for Treatment of Non-Small Cell Lung Cancer and Melanoma Select patients with Stage II to IIIA non-small cell lung cancer for treatment with TECENTRIQ as a single agent based on PD-L1 expression on tumor cells.

Select patients with first-line metastatic non-small cell lung cancer for treatment with TECENTRIQ as a single agent based on the PD-L1 expression on tumor cells or on tumor-infiltrating immune cells.

Information on FDA-approved tests for the determination of PD-L1 expression in metastatic non-small cell lung cancer are available at: Select patients with unresectable or metastatic melanoma for treatment with TECENTRIQ in combination with cobimetinib and vemurafenib after confirming the presence of a BRAF V600 mutation.

Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: 2.2 Recommended Dosage The recommended dosages of TECENTRIQ are presented in Table 1.

TECENTRIQ as an intravenous infusion over 60 minutes.

Table 1: Recommended Dosage of TECENTRIQ as a Single Agent Indication Recommended Dosage of TECENTRIQ Duration of Therapy Metastatic NSCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Until disease progression or unacceptable toxicity Adjuvant Treatment of NSCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Up to one year, unless there is disease recurrence or unacceptable toxicity ASPS (adult) 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Until disease progression or unacceptable toxicity ASPS (pediatric, 2 years of age and older) 15 mg/kg (up to a maximum 1200 mg) every 3 weeks The recommended intravenous dosages of TECENTRIQ in combination with other therapeutic agents are presented in Table 2.

Refer to the respective Prescribing

Information for each therapeutic agent administered in combination with TECENTRIQ for the recommended dosage information, as appropriate.

Table 2: Recommended Dosage of TECENTRIQ in Combination with Other Therapeutic Agents Indication Recommended Dosage of TECENTRIQ Duration of Therapy NSCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Administer TECENTRIQ prior to chemotherapy and bevacizumab when given on the same day. Until disease progression or unacceptable toxicity SCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Administer TECENTRIQ prior to chemotherapy when given on the same day. HCC 840 mg every 2 weeks or 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 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Administer TECENTRIQ with cobimetinib 60 mg orally once daily (21 days on and 7 days off) and vemurafenib 720 mg orally twice daily.

Prior to initiating

TECENTRIQ, patients should receive a 28-day treatment cycle of cobimetinib 60 mg orally once daily (21 days on and 7 days off) and vemurafenib 960 mg orally twice daily from Days 1-21 and vemurafenib 720 mg orally twice daily from Days 22-28. 2.3 Dosage Modifications for Adverse Reactions No dose reduction for TECENTRIQ is recommended.

In general, withhold TECENTRIQ for severe (Grade 3) immune-mediated adverse reactions.

Permanently discontinue

TECENTRIQ for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids.

Dosage modifications for

TECENTRIQ for adverse reactions that require management different from these general guidelines are summarized in Table 3.

Table 3: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Based on Common Terminology Criteria for Adverse Events (CTCAE), version 4 Dosage Modification ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson syndrome, TEN = toxic epidermal necrolysis Immune-Mediated Adverse Reactions Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade to 1) after corticosteroid taper.

Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids Grades 3 or 4 Permanently discontinue Colitis Grades 2 or 3 Withhold Grade 4 Permanently discontinue Hepatitis with no tumor involvement of the liver AST or ALT increases to more than and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue TECENTRIQ based on recommendations for hepatitis with no liver involvement Baseline AST or ALT is more than and up to 3 times ULN and increases to more than and up to 10 times ULN or Baseline AST or ALT is more than and up to 5 times ULN and increases to more than and up to 10 times ULN Withhold AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Grades 3 or 4 Withhold until clinically stable or permanently discontinue depending on severity Nephritis with Renal Dysfunction Grades 2 or 3 increased blood creatinine Withhold Grade 4 increased blood creatinine Permanently discontinue Exfoliative Dermatologic Conditions Suspected SJS, TEN, or DRESS Withhold Confirmed SJS, TEN, or DRESS Permanently discontinue Myocarditis or Pericarditis Grades 2, 3, or 4 Permanently discontinue Neurological Toxicities Grade 2 Withhold Grades 3 or 4 Permanently discontinue Other Adverse Reactions Infusion-Related Reactions Grades 1 or 2 Interrupt or slow the rate of infusion Grades 3 or 4 Permanently discontinue 2.4 Preparation and Administration Preparation Visually inspect drug product for particulate matter and discoloration prior to administration, whenever solution and container permit.

Discard the vial if the solution is cloudy, discolored, or visible particles are observed.

Do not shake the vial.

Prepare the solution for infusion as follows: Select the appropriate vial(s) based on the prescribed dose.

Withdraw the required volume of

TECENTRIQ from the vial(s) using sterile needle and syringe.

Dilute to a final concentration between 3.2 mg/mL and 16.8 mg/mL in a polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag containing 0.9% Sodium Chloride Injection, USP.

Dilute with only 0.9% Sodium Chloride Injection, USP.

Mix diluted solution by gentle inversion.

Do not shake.

Discard used or empty vials of

This product does not contain a preservative.

Administer immediately once prepared.

If diluted

TECENTRIQ infusion solution is not used immediately, store solution either: At room temperature for no more than 6 hours from the time of preparation.

This includes room temperature storage of the infusion in the infusion bag and time for administration of the infusion, or Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 7 days from time of preparation.

Do not freeze.

Administer the initial infusion over 60 minutes through an intravenous line with or without a sterile, non-pyrogenic, low-protein binding in-line filter (pore size of 0.2–0.22 micron).

Do not coadminister other drugs through the same intravenous line.

Do not administer as an intravenous push or bolus.

injection is a sterile, preservative-free, and colorless to slightly yellow solution for intravenous infusion supplied as a carton containing one 840 mg/14 mL single-dose vial (NDC 50242-918-01) or 1,200 mg/20 mL single-dose vial (NDC 50242-917-01).

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original carton to protect from light.

Do not freeze.

Do not shake.

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original carton to protect from light.

Do not freeze.

Do not shake.

Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman.

There are no available data on the use of TECENTRIQ in pregnant women.

Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus resulting in fetal death.

Advise females of reproductive potential of the potential risk to a fetus.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Animal reproduction studies have not been conducted with TECENTRIQ to evaluate its effect on reproduction and fetal development.

A literature-based assessment of the effects on reproduction demonstrated that a central function of the PD-L1/PD-1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to a fetus.

Blockage of

PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to a fetus and to result in an increase in fetal loss; therefore, potential risks of administering TECENTRIQ during pregnancy include increased rates of abortion or stillbirth.

As reported in the literature, there were no malformations related to the blockade of PD-L1/PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice.

Based on its mechanism of action, fetal exposure to atezolizumab may increase the risk of developing immune-mediated disorders or altering the normal immune response.

Alveolar Soft Part Sarcoma The safety and effectiveness of TECENTRIQ for unresectable or metastatic ASPS have been established in pediatric patients aged 2 years and older.

Use of

TECENTRIQ for this indication is supported by evidence from an adequate and well controlled study of TECENTRIQ in adults and 2 adolescent pediatric patients (≥12 years of age) with ASPS with additional pharmacokinetic and safety data in pediatric patients 2 years to <17 years.

These data suggest that atezolizumab exposure in pediatric patients aged 2 years and older is comparable with that of adults and is expected to result in similar safety and efficacy to that of adults.

The course of unresectable or metastatic

ASPS is sufficiently similar between pediatric patients to 11 years old and that of adults and adolescent patients to allow extrapolation of efficacy and safety to pediatric patients 2 years and older.

The safety and effectiveness of TECENTRIQ for ASPS have not been established in pediatric patients younger than 2 years of age.

Solid Tumors and Lymphomas The safety and effectiveness of TECENTRIQ in pediatric patients have not been established in non-small cell lung cancer, small-cell lung cancer, hepatocellular carcinoma, or melanoma.

The safety and effectiveness of

TECENTRIQ were assessed, but not established in a single-arm, multi-center, multi-cohort trial (NCT02541604) in 60 pediatric patients aged 7 months to <17 years with relapsed or progressive solid tumors and lymphomas.

No new safety signals were observed in pediatric patients in this study.

TECENTRIQ as a Single-Agent

Of 2616 patients with metastatic NSCLC and other tumor types treated with single agent TECENTRIQ in clinical studies, 49% were 65 years and over and 15% were 75 years and over.

No overall differences in safety or effectiveness were observed between patients aged 65 years or older and younger patients.

TECENTRIQ in Combination with Other Antineoplastic Drugs Of 2421 patients with NSCLC and SCLC treated with TECENTRIQ in combination with other antineoplastic drugs in clinical studies, 48% were 65 years and over and 10% were 75 years and over.

Of the 242 patients with ES-SCLC treated with TECENTRIQ in combination with lurbinectedin in IMforte, 124 (51%) patients were 65 years of age and older, while 29 (12%) patients were 75 years of age and older.

No overall differences in effectiveness were observed between older and younger patients.

There was a higher incidence of

Grade 3 or 4 adverse reactions (45% vs 31%) and treatment discontinuation (11% vs 0.8%) in patients ≥ 65 years of age compared to younger patients, respectively.