Dosing and uses of Tecentriq (atezolizumab)
Adult dosage forms and strengths
IV solution
- 1200mg/20mL (60mg/mL)
Urothelial Carcinoma
Indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy, or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
1200 mg IV q3wk infused over 60 min until disease progression or unacceptable toxicity
If the first infusion is tolerated, all subsequent infusions may be administered IV over 30 min
See Administration
Non-Small Cell Lung Cancer
Indicated for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression 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
1200 mg IV q3wk infused over 60 min until disease progression or unacceptable toxicity
If the first infusion is tolerated, all subsequent infusions may be administered IV over 30 min
See Administration
Dosage modifications
No dose reductions are recommended
Withhold dose for any of the following:
- AST or ALT >3 and up to 5 x ULN, or total bilirubin >1.5 and up to 3 x ULN
- Grade 2 or 3 diarrhea or colitis
- Symptomatic hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, or grade 3 or 4 hyperglycemia
- Grade 2 ocular inflammatory toxicity
- Grade 2 or 3 pancreatitis or grade 3 or 4 increases in amylase or lipase levels (ie, >2 x ULN)
- Grade 3 or 4 infection
- Grade 2 infusion-related reactions
- Grade 3 rash
- May resume dosing in patients whose adverse reactions recover to grade 0-1
Permanently discontinue
- Grade 3 or 4 pneumonitis
- AST or ALT >5 x ULN or total bilirubin >3 x ULN
- Grade 4 diarrhea or colitis
- Grade 4 hypophysitis
- Myasthenic syndrome/myasthenia gravis, Guillain-Barré, or meningoencephalitis
- Grade 3 or 4 ocular inflammatory toxicity
- Grade 4 or any grade of recurrent pancreatitis
- Grade 3 or 4 infusion-related reactions
- Grade 4 rash
Renal impairment
- No dose adjustment is recommended
Hepatic impairment
- Mild: No dose adjustment is recommended
- Moderate-to-severe: Not studied
Dosing Considerations
Approved under accelerated approval based on tumor response rate and durability of response
Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials
Ventana PD-L1 is a complementary diagnostic assay to provide PD-L1 status on patients who are considering treatment with atezolizumaB
Small Cell Lung Cancer (Orphan)
Orphan designation for treatment of small cell lung cancer
Sponsor
- Genentech, Inc; 1 DNA Way; South San Francisco, California 94080
Pediatric dosage forms and strengths
Safety and efficacy not established
Tecentriq (atezolizumab) adverse (side) effects
>10%
All grades unless otherwise stated
Fatigue (52%)
Decreased appetite (26%)
Nausea (25%)
Urinary tract infection (22%)
Constipation (21%)
Pyrexia (21%)
Diarrhea (18%)
Peripheral edema (18%)
Abdominal pain (17%)
Vomiting (17%)
Dyspnea (16%)
Back/neck pain (15%)
Rash (15%)
Arthralgia (14%)
Pruritus (13%)
1-10%
All are grades 3-4
Lymphopenia (10%)
Hyponatremia (10%)
Anemia (8%)
Hyperglycemia (5%)
Increased alkaline phosphatase (4%)
Increased creatinine (3%)
Increased ALT (2%)
Increased AST (2%)
Hypoalbuminemia (1%)
Warnings
Contraindications
None
Cautions
Withhold for moderate and permanently discontinue for severe or life-threatening pneumonitis
Monitor for changes in liver function; withhold for moderate and permanently discontinue for severe or life-threatening transaminase or total bilirubin elevation
Withhold for moderate or severe, and permanently discontinue for life-threatening colitis
Immune-related myasthenic syndrome/myasthenia gravis, Guillain Barré, or meningoencephalitis: Permanently discontinue for any grade
Withhold for moderate and permanently discontinue for severe ocular inflammatory toxicity
Withhold for moderate or severe, and permanently discontinue for life-threatening pancreatitis, or any grade of recurring pancreatitis
Withhold for severe or life-threatening infection
Interrupt or slow the rate of infusion for mild or moderate infusion reactions and discontinue for severe or life-threatening infusion reactions
Can cause fetal harm; advise females of reproductive potential of the potential risk to a fetus and use of effective contraception
Immune-related endocrinopathies
- Hypophysitis: Withhold for moderate or severe and permanently discontinue for life-threatening hypophysitis
- Thyroid disorders: Monitor for changes in thyroid function; withhold for symptomatic thyroid disease
- Adrenal insufficiency: Withhold for symptomatic adrenal insufficiency
- Type 1 diabetes mellitus: Withhold for ≥grade 3 hyperglycemia
Pregnancy
Pregnancy
Based on its mechanism of action, can cause fetal harm when administered during pregnancy; advise females of reproductive potential to use effective contraception during treatment and for at least 5 months following the last dose
Based on animal studies, atezolizumab may impair fertility in females of reproductive potential while receiving treatment
Lactation
Unknown if distributed in human breast milk
Advise lactating woman not to breastfeed during treatment and for at least 5 months after the last dose
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tecentriq (atezolizumab)
Mechanism of action
Monoclonal antibody to programmed cell death ligand-1 protein (PDL1); binding PDL1 blocks the interaction between PDL-1 and its ligands (including B7.1 receptors)
PDL-1
- PDL1 is expressed on the surface of activated T cells under normal conditions; binding PDL1 inhibits immune activation and reduces T-cell cytotoxic activity when bound
- This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation
- Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PDL1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells
Absorption
Systemic accumulation over 2-3 cycles of repeated dosing
- Peak plasma concentration: 1.91-fold
- Minimum plasma concentration: 1.46-fold
- AUC: 2.75-fold
Distribution
Vd: 6.9 L
Elimination
Half-life: 27 days
Clearance: 0.2 L/day
Administration
IV Preparation
Visually inspect drug product for particulate matter and discoloration prior to administration
Solution should appear colorless to slightly yellow
Discard if the solution is cloudy, discolored, or visible particles are observed
Do NOT shake the viaL
Dilution
- Withdraw 20 mL of solution from the vial
- Dilute into a 250-mL polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag containing 0.9% NaCl
- Dilute with 0.9% NaCl only
- Mix diluted solution by gentle inversion; do not shake
- Discard partially used or empty vial
IV Administration
For IV infusion only; do not give as IV bolus or IV push
Administer through an IV line with or without a sterile, nonpyrogenic, low-protein binding in-line filter (pore size of 0.2–0.22 micron)
First IV infusion: Infuse over 60 min
Subsequent IV infusions: If first infusion is tolerated, may administer subsequent doses over 30 min
Do not coadminister with other drugs through the same IV line
Storage
Contains no preservatives
Do not freeze undiluted or diluted solution
Do not shake undiluted or diluted solution
Unopened vials
- Refrigerate at 2-8°C (36-46°F) in original carton to protect from light
Diluted infusion solution
- Administer immediately once prepared
- If not used immediately, it can be stored by either:
- At room temperature for <6 hr from time of preparation (includes infusion time) OR
- Refrigerate at 2-8°C (36-46°F) for no more than 24 hr
