Atezolizumab

Atezolizumab is used for: Metastatic non-small cell lung cancer, who have disease progression during or following platinum-containing chemotherapy.

General: Atezolizumab must be administered as an intravenous (IV) infusion under the supervision of a qualified healthcare professional. Do not administer as an IV push or bolus. Substitution by any other biological medicinal product requires the consent of the prescribing physician. The recommended dose is 1200 mg administered by IV infusion every three weeks. The initial dose of Atezolizumab must be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes. Duration of treatment: Patients are treated with Atezolizumab until loss of clinical benefit or unmanageable toxicity. Hepatic impairment: Based on a population pharmacokinetic analysis, no dose adjustment is required for patients with mild hepatic impairment. There are no data in patients with moderate or severe hepatic impairment

Renal impairment: Based on a population pharmacokinetic analysis, no dose adjustment is required in patients with renal impairment

IV Preparation Dilution Withdraw required amount from 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 Gently invert diluted solution; 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 When administering in combination with chemotherapy, administer atezolizumab before chemotherapy when given on the same day Do not co-administer with other drugs through the same IV line

Atezolizumabis contraindicated in patients with a known hypersensitivity to atezolizumab or any of the excipients.

Immune-mediated pneumonitis or interstitial lung disease occurred; monitor for signs and symptoms of pneumonitis; administer steroids at a dose of 1-2 mg/kg/day prednisone equivalents for Grade >2 pneumonitis, followed by corticosteroid taper 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; administer corticosteroids, prednisone 1-2 mg/kg/day or equivalents, followed by a taper for Grade 2 or higher elevations of ALT, AST, and/or total bilirubin Immune-mediated colitis or diarrhea reported; if symptoms persist for >5 days or recur, administer 1-2 mg/kg prednisone or equivalent per day; withhold treatment for Grade 3 diarrhea or colitis; treat with IV methyl prednisolone 1-2 mg/kg per day and convert to oral steroids once patient improves Can cause fetal harm; advise females of reproductive potential of potential risk to a fetus and use of effective contraception. Lactation Unknown if distributed in human breast milk As human IgG is excreted in human milk, potential for absorption and harm to the infant is unknown Advise lactating woman not to breastfeed during treatment and for at least 5 months after the last dose

Pregnancy Based on its mechanism of action, can cause fetal harm when administered during pregnancy No available data on use in pregnant women Animal data 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 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, potential for absorption and harm to the infant is unknown Advise lactating woman not to breastfeed during treatment and for at least 5 months after the last dose

Side effects of Atezolizumab : >10% (Urothelial carcinoma) Fatigue (52%) Decreased appetite (24-26%) Nausea (22-25%) Diarrhea (18-24%) Urinary tract infection (17-22%) Constipation (15-21%) Pyrexia (14-21%) Back/neck pain (15-18%) Pruritus (13-18%) Peripheral edema (17-18%) Rash (15-17%) Vomiting (16-17%) Abdominal pain (15-17%) Dyspnea (12-16%) Cough (14%) Hyponatremia, Grade 3 or 4 (15%) Arthralgia (13-14%) Hematuria (14%) >10% (NSCLC, in combination with bevacizumab, paclitaxel, and carboplatin) Anemia (67-83%) Hyperglycemia (61%) Neuropathy (56%) Increased BUN (52%) Neutropenia (52%) Fatigue/asthenia (44-50%) Lymphocytopenia (49%) Alopecia (48%) Lymphopenia (48%) Hypoalbuminemia (40-48%) Hyponatremia (38-42%) Myalgia/pain (42%) Hypomagnesemia (26-42%) Increased AST (31-40%) Nausea (18-39%) Increased alkaline phosphatase (39%) Increased ALT (27-37%) Diarrhea (16-33%) Neutropenia, Grade 3 or 4 (31%) Increased TSH (30%) Constipation (18-30%) Decreased appetite (23-29%) Hyperkalemia (28%) Increased creatinine (23-28%) Hypocalcemia (26%) Arthralgia (26%) Cough (20-26%) Hypertension (25%) Hyperphosphatemia (25%) Hypophosphatemia (25%) Hypokalemia (23%) Rash (12-23%) Dyspnea (22%) Pyrexia (18-19%) Vomiting (19%) Epistaxis (17%) Lymphopenia, Grade 3 or 4 (17%) Proteinuria (16%) Headache (16%) Arthralgia (1-12%) >10% (TNBC) Alopecia (56%) Fatigue (47%) Peripheral neuropathies (47%) Nausea (46%) Diarrhea (33%) Anemia (28%) Constipation (25%) Headache (23%) Neutropenia (21%) Vomiting (20%) Decreased appetite (20%) Pyrexia (19%) Arthralgia (18%) Rash (17%) Peripheral edema (15%) Back pain (15%) Myalgia (14%) Pruritus (14%) Dizziness (14%) Dysgeusia (14%) Hypothyroidism (14%) Decreased neutrophils (13%) Urinary tract infection (12%) Asthenia (12%) Pain in extremity (11%) Upper respiratory infection (11%) Nasopharangitis (11%) >10% (SCLC) Anemia (94%) Neutropenia (73%) Hyperglycemia (67%) Thrombocytopenia (58%) Lymphopenia (46%) Neutropenia, Grade 3-4 (45%) Increased alkaline phosphatase (38%) Fatigue/asthenia (39%) Nausea (38%) Alopecia (37%) Hyponatremia (34%) Hypoalbuminemia (32%) Hypomagnesemia (31%) Decreased TSH (28%) Decreased appetite (27%) Constipation (26%) Hypocalcemia (26%) Increased ALT (26%) Increased AST (22%) Increased blood creatinine (22%) Neutropenia (22%) Hyperphosphatemia (21%) Increased TSH (21%) Thrombocytopenia, Grade 3-4 (20%) Vomiting (20%) Anemia, Grade 3-4 (17%) Hyponatremia, Grade 3-4 (15%) Lymphopenia, Grade 3-4 (14%) Hyperglycemia, Grade 3-4 (10%)

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