Atezolizumab

Atezolizumab is a prescription medication used to treat the symptoms of melanoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, and urothelial carcinoma. 

• Atezolizumab is available under the following different brand names: Tecentriq

Adult dosage

Injectable solution

• 60mg/mL (1200mg/20mL)

Non-Small Cell Lung Cancer

Adult dosage

Single-agent

• 840 mg IV every 2 weeks or
• 1200 mg IV every 3 weeks or
• 1680 mg IV every 4 weeks
• Continue for up to 1 year OR unless disease progression or unacceptable toxicity

Metastatic NSCLC

• 840 mg IV every 2 weeks or
• 1200 mg IV every 3 weeks or
• 1680 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Combination therapy with bevacizumab, paclitaxel, and carboplatin

• 1200 mg IV on Day 1 every 3 weeks plus bevacizumab, paclitaxel, and carboplatin x 4-6 cycles
• After completion of chemotherapy cycles 4-6 with bevacizumab
  • Atezolizumab 1200 mg IV, followed by bevacizumab on Day 1 every 3 weeks; continue until disease progression or unacceptable toxicity
• Atezolizumab dose following completion of 4-6 cycles, and if bevacizumab is discontinued
  • 840 mg IV every 2 weeks or
  • 1200 mg IV every 3 weeks or
  • 1680 mg IV every 4 weeks
  • Continue until disease progression or unacceptable toxicity

Combination therapy with paclitaxel protein-bound and carboplatin

• Atezolizumab 1200 mg on day 1 every 3 weeks plus paclitaxel protein-bound and carboplatin x 4-6 cycles for each 21-day cycle
• Atezolizumab dose following completion of 4-6 cycles
  • 840 mg IV every 2 weeks or
  • 1200 mg IV every 3 weeks or
  • 1680 mg IV every 4 weeks
  • Continue until disease progression or unacceptable toxicity

Small Cell Lung Cancer

Adult dosage

• 1200 mg IV on Day 1 every 3 weeks
• Continue until disease progression or unacceptable toxicity

Following completion of 4 cycles of carboplatin and etoposide

• 840 mg IV every 2 weeks or
• 1200 mg IV every 3 weeks or
• 1680 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Hepatocellular Carcinoma

Adult dosage

• Atezolizumab 1200 mg IV on Day 1 (administered before bevacizumab), plus
• Bevacizumab 15 mg/kg IV on Day 1
• Repeat every 3 weeks until disease progression or unacceptable toxicity

Atezolizumab dose if bevacizumab discontinued for toxicity

• 840 mg IV every 2 weeks or
• 1200 mg IV every 3 weeks or
• 1680 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Melanoma

Adult dosage

• Each cycle is 28 days
• Before initiating atezolizumab
  • Cobimetinib: 60 mg orally once daily on Days 1-21, PLUS
  • Vemurafenib: 960 mg orally twice a day on Days 1-21, THEN, 720 mg orally twice a day on Days 22-28
• Cycle 1 and onwards
  • Atezolizumab 840 mg IV on Days 1 and 15, PLUS
  • Cobimetinib 60 mg orally once daily on Days 1-21 plus vemurafenib 720 mg orally twice a day  on Days 1-28
  • Continue until disease progression or unacceptable toxicity

Urothelial Carcinoma

Adult dosage

• 840 mg IV every 2 weeks or
• 1200 mg IV every 3 weeks or
• 1680 mg IV every 4 weeks
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Atezolizumab include:

• back, neck, arm, or leg pain,
• difficulty moving,
• loss of or change in taste,
• thinning of the hair,
• hair loss,
• unsteadiness,
• awkwardness, and
• weakness in the arms, hands, legs, or feet.

Serious side effects of Atezolizumab include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• nausea,
• nosebleed,
• blurred vision,
• rapid weight gain,
• constipation,
• cough,
• diarrhea,
• burning or painful urination,
• dizziness,
• earache,
• fever,
• slow or fast heartbeat,
• sore throat,
• stuffy or runny nose,
• tightness in the chest,
• tingling of the hands, arms, legs, or feet,
• frequent urge to urinate,
• weakness,
• tiredness,
• headache,
• loss of appetite,
• sores or white spots in the mouth,
• unusual bleeding or bruising,
• vomiting,
• anxiety,
• confusion,
• depression,
• difficulty chewing, swallowing, or talking,
• dry skin and hair,
• irritability,
• clay-colored stools,
• muscle cramp and stiffness,
• rapid or shallow breathing,
• seizures,
• trouble sleeping,
• yellowing of eyes and skin (jaundice),
• blistering, peeling, or loosening of the skin,
• Red skin lesions with a purple center,
• fruit-like breath odor, and
• sweating

Rare side effects of Atezolizumab include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first,

• Atezolizumab has no noted severe interactions with any other drugs.
• Atezolizumab has no noted serious interactions with any other drugs.
• Atezolizumab has no noted moderate interactions with any other drugs.
• Atezolizumab has no noted minor interactions with any other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Atezolizumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Atezolizumab?”

Cautions

• Immune-mediated pneumonitis or interstitial lung disease occurred; monitor for signs and symptoms of pneumonitis; incidence of pneumonitis is higher in patients who have received thoracic radiation
• May cause liver test abnormalities and immune-mediated hepatitis; fatal cases reported; monitor for signs and symptoms of hepatitis, during and after discontinuation of therapy, including clinical chemistry monitoring
• Immune-mediated colitis or diarrhea reported
• May cause severe or life-threatening infusion-related reactions; monitor for signs and symptoms of infusion-related reactions
• Severe infections (eg, sepsis, herpes encephalitis, mycobacterial infection) leading to retroperitoneal hemorrhage were reported; the most common infection was upper respiratory tract infection; monitor for signs and symptoms of infection
• Hematologic/immune effects may include hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection
• Uveitis, iritis, and other ocular inflammatory toxicities can occur; some cases can be associated with retinal detachment; various grades of visual impairment, including blindness, can occur; if uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss
• Do not substitute paclitaxel protein-bound with paclitaxel in combination with the drug in clinical practice for metastatic TNBC outside of controlled trials
• Can cause fetal harm; advise females of reproductive age of the potential risk to a fetus and use of effective contraception
• Immune-related endocrinopathies
  • Immune-related myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, or meningoencephalitis reported; permanently discontinue for any grade
  • Monitor for clinical signs and symptoms of meningitis or encephalitis
  • Monitor for symptoms of motor and sensory neuropathy
  • Symptomatic pancreatitis without an alternative etiology occurred in 0.1% of patients across clinical trials; pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; monitor for signs and symptoms of acute pancreatitis
  • Monitor for signs and symptoms of myocarditis
  • Thyroid disorders may occur; thyroiditis can present with or without endocrinopathy; not reported to lead to permanent discontinuation; hypothyroidism can follow hyperthyroidism monitor thyroid function before and periodically during treatment; initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated; continue therapy for hypothyroidism and interrupt for hyperthyroidism or permanently discontinue therapy based on the severity
  • Adrenal insufficiency may occur; monitor patients for clinical signs and symptoms of adrenal insufficiency
  • Type 1 diabetes mellitus reported; monitor for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated; interrupt treatment based on the severity
  • Myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatic reported
  • Hypoparathyroidism may occur
  • Hypophysitis/hypopituitarism may occur; hypophysitis can present with acute symptoms associated with mass effects such as headache, photophobia, or visual field cuts; hypophysitis can cause hypopituitarism; withhold or permanently discontinue therapy depending on severity; for Grade 2 or higher hypophysitis, initiate prednisone 1-2 mg/kg/day or equivalents, followed by a taper and hormone replacement therapy as clinically indicated
• FDA Safety Alert
  • On 9/8/2020, FDA alerted health care professionals, oncology clinical investigators, and patients that the combination of atezolizumab and paclitaxel in previously untreated inoperable locally advanced or metastatic TNBC was ineffective
  • Alert was based on results from the IMpassion131 trial, a double-blind, multicenter, placebo-controlled trial comparing atezolizumab or placebo in combination with paclitaxel for patients with metastatic TNBC
  • In this trial, atezolizumab and paclitaxel did not significantly reduce the risk of cancer progression and death compared with placebo and paclitaxel in the PD-L1-positive population
  • An increase in the risk of death observed in patients treated with atezolizumab plus paclitaxel compared with placebo and paclitaxel in the PD-L1-positive population; the efficacy of atezolizumab in combination with paclitaxel in patients with unresectable locally advanced or metastatic TNBC has not been demonstrated
  • Interim overall survival results favored paclitaxel and placebo, over paclitaxel and atezolizumab in both the PD-L1-positive population and total population
• Immune-mediated adverse reactions
  • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue; reactions can occur at any time after starting a PD1/PD-L1 blocking antibody
  • While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies
  • Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies; monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions
  • Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment; in cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection
  • Institute medical management promptly, including specialty consultation as appropriate; withhold or permanently discontinue therapy depending on severity; in general, if therapy requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less
  • Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month; consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy
• Complications of allogeneic HSCT
  • Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody
  • Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
  • These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
  • Follow patients closely for evidence of transplant-related complications and intervene promptly; consider benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT
• Colitis
  • The drug can cause immune-mediated colitis that can present with diarrhea, abdominal pain, and lower gastrointestinal (GI) bleeding
  • Cytomegalovirus (CMV) infection/ reactivation reported in patients with corticosteroid-refractory immune-mediated colitis
  • In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies

Pregnancy and Lactation

• Based on its mechanism of action, can cause fetal harm when administered during pregnancy
• No available data on use in pregnant women 
• Contraception
  • Advise females of reproductive potential to use effective contraception during treatment and for at least 5 months following the last dose
• Infertility
  • Based on animal studies, atezolizumab may impair fertility in females of reproductive potential while receiving treatment

Lactation

• Unknown if distributed in human breast milk
• As human IgG is excreted in human milk, the potential for absorption and harm to the infant is unknown
• Advise a lactating woman not to breastfeed during treatment and for at least 5 months after the last dose