Atezolizumab

Drug Class: Immune checkpoint inhibitor – Anti–PD-L1 monoclonal antibody

Mechanism of Action

Selectively binds programmed death-ligand 1 (PD-L1), blocking interaction with PD-1 and B7.1 receptors. This prevents PD-L1–mediated immune suppression, restoring T-cell activity against tumor cells. Unlike PD-1 inhibitors, it leaves PD-L2–PD-1 interaction intact, potentially reducing some immune toxicities.

Indications (Canada/US)

• NSCLC – 1L in combination or 2L after platinum-based chemo
• Extensive-stage SCLC – 1L with carboplatin + etoposide
• Triple-negative breast cancer (TNBC) – PD-L1+ unresectable locally advanced/metastatic, with nab-paclitaxel
• Hepatocellular carcinoma (HCC) – with bevacizumab, untreated advanced/unresectable
• Urothelial carcinoma – Locally advanced/metastatic post-platinum or cisplatin-ineligible PD-L1+ (Check formulary and PD-L1 testing requirements)

Dosing (Adult)

• 840 mg IV q2 weeks
• 1200 mg IV q3 weeks
• 1680 mg IV q4 weeks
• Infuse over 60 minutes (first dose), then ≥30 minutes if tolerated. No dose adjustments for renal/mild hepatic impairment.

Pharmacokinetics

• t½ ~ 27 days
• Linear PK, steady state ~16 weeks
• Catabolized via nonspecific IgG pathways; not CYP-dependent

Key Toxicities (Immune-Mediated)

• Dermatologic: rash, pruritus
• Endocrine: hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, type 1 DM
• GI: colitis
• Pulmonary: pneumonitis
• Hepatic: hepatitis (↑ AST/ALT, bilirubin)
• Rare: myocarditis, nephritis

Management of Toxicities

• Grade 1 → continue with close monitoring
• Grade 2 → hold; start prednisone 0.5–1 mg/kg/day
• Grade ≥3 → permanently discontinue; prednisone 1–2 mg/kg/day ± slow taper ≥4 weeks
• Rule out infection before starting steroids

Monitoring

• Baseline & periodic TSH, free T4, cortisol, fasting glucose
• LFTs and bilirubin prior to each cycle
• Renal function
• Signs of colitis, pneumonitis, hepatitis, endocrinopathies
• PD-L1 testing for some indications

Counseling Points

• Explain delayed onset of benefit and risk of late immune-related adverse events (can occur months after discontinuation)
• Report new cough, diarrhea, rash, fatigue, headaches, or vision changes immediately
• Avoid live vaccines during treatment
• Effective contraception during and ≥5 months post-treatment

Clinical Pearls

• Do not substitute with PD-1 inhibitors dose-for-dose — different targets and efficacy profiles
• When combined with bevacizumab in HCC, monitor for additive bleeding/hypertension risks
• Infusion reactions are rare but possible — premedication generally not required
• Not effective in all PD-L1+ tumors — biomarker is predictive but imperfect