Generic Name

Tecentriq

Mechanism

• PD‑1 Blockade: *Tecentriq* binds with high affinity to PD‑1 receptors on activated T‑cells, preventing interaction with its ligands PD‑L1 and PD‑L2 expressed on tumor cells and antigen‑presenting cells.
• Reinvigoration of T‑cell activity: By interrupting the inhibitory signal, it restores cytokine production (IFN‑γ, TNF‑α) and promotes cytotoxic T‑cell proliferation and tumor infiltration.
• Selective Immune Modulation: The pharmacologic effect is selective for activated T‑cells, reducing systemic immune activation compared with conventional chemotherapy.

Pharmacokinetics

Indications

• Non‑small‑cell lung cancer (NSCLC) – first‑line plus second‑line in PD‑L1 ≥ 50% expressing tumors; squamous and non‑squamous subtypes.
• Urothelial carcinoma – first‑line in metastatic disease or platinum‑unfit patients.
• Melanoma – for progression after ipilimumab or as first‑line.
• Head and neck squamous cell carcinoma (HNSCC) – recurrent/metastatic disease.
• Hepatocellular carcinoma (HCC) – in combination with atezolizumab + bevacizumab.
• Triple‑negative breast cancer (TNBC) – first‑line in metastatic (KEYNOTE‑355).
• Endometrial carcinoma – in tumors with high microsatellite instability (MSI‑H)/deficient mismatch repair (dMMR).
• Other indications: Hodgkin lymphoma, renal cell carcinoma, Merkel cell carcinoma, cervical cancer, and others per FDA/EMA labeling or companion‑diagnostic guidance.

Contraindications

• Contraindications:
• Active autoimmune disease requiring systemic therapy (e.g., severe rheumatoid arthritis, systemic lupus).
• Concurrent systemic immunosuppressive therapy other than low‑dose steroids (≤10 mg prednisone equivalent).
• Warnings:
• Immune‑related adverse events (irAEs) – including colitis, hepatitis, pneumonitis, endocrinopathies (hypothyroidism, adrenal insufficiency), nephritis, and dermatitis.
• Cardiac toxicity – rare myocarditis or pericarditis; monitor troponin and ECG as indicated.
• Infections – opportunistic infections (TB, fungal) possible, especially post‑treatment.
• Hypersensitivity – anaphylaxis can occur; premedication not routinely recommended unless prior reaction.

Dosing

• Standard dose: 200 mg IV over 30 min every 3 weeks (or 400 mg IV every 6 weeks) – the 3‑week regimen is more common.
• Alternative: 1.25 mg/kg IV every 3 weeks (historically used for patients needing weight‑based precision).
• Infusion settings:
• Pre‑medication with acetaminophen and antihistamine routinely to reduce infusion‑related reactions.
• Monitor vitals during the first 2 hours of infusion.
• Duration: Treatment continues until disease progression, unacceptable toxicity, or up to 2 years (if no progression) per label.

Adverse Effects

Monitoring

• Before each cycle
• CBC, CMP, fasting glucose, serum creatinine, thyroid panel.
• Baseline imaging (CT/PET) per protocol.
• While on therapy
• Infusion reaction monitoring: vitals 30 min pre‑ and during infusion.
• Endocrine: TSH, free T4, cortisol (if adrenal insufficiency suspected).
• Pulmonary: baseline and periodic chest imaging or pulmonary function tests if symptoms arise.
• Gastrointestinal: monitor stool frequency for diarrhea and stool color for occult bleeding.
• Liver Function: LFTs every 2–3 weeks in first 2 months, then q3–4 weeks.
• Renal: serum creatinine and urinalysis for protein/creatinine ratio.
• Special:
• Patients with prior autoimmune disease: consider baseline organ function tests more frequently.
• Pregnancy: teratogenicity data insufficient; contraindicated.

Clinical Pearls

• Toxicity Management – Early recognition and prompt corticosteroid therapy can reverse most irAEs; consider a 0.5–1 mg/kg prednisone for grade 2, 1–2 mg/kg for grade 3–4, taper over at least 4–6 weeks.
• Checkpoint synergy – When combining *Tecentriq* with CTLA‑4 inhibitors (e.g., ipilimumab), hold *Tecentriq* for ≥10 days after any steroid dose >10 mg prednisone before restarting.
• Dosing flexibility – The 6‑week regimen (400 mg) reduces infusion frequency, improving compliance without compromising efficacy per KEYNOTE‑024.
• Inflammatory Biomarkers – Elevated baseline CRP and IL‑6 may predict higher irAE risk; monitor closely in high‑risk patients.
• Checkpoint‑related Pneumonitis – Present with dyspnea, cough, and low‑grade fever; early high‑dose steroids (methylprednisolone 1–2 mg/kg) and imaging can expedite recovery.
• Adjuvant Setting – In early‑stage melanoma or NSCLC, adjuvant *Tecentriq* improves disease‑free survival but requires lifelong surveillance for irAEs.
• Drug Interactions – No clinically relevant drug–drug interactions as *Tecentriq* is not metabolized by CYP enzymes; however, concomitant agents causing autoimmune flares (e.g., TNF‑α inhibitors) warrant caution.
• Vaccination – Live vaccines are contraindicated; inactivated vaccines can be administered safely, but efficacy may be diminished—plan vaccination schedules accordingly.

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• Key pharmacology take‑home:
• *Tecentriq* expands checkpoint blockade into multiple oncologic indications, hinging on PD‑1 pathway inhibition.
• Weight‑neutral, long half‑life dosing simplifies regimens.
• Vigilant monitoring for irAEs is essential – early intervention with steroids preserves both safety and treatment continuation.

This concise drug card is tailored for quick reference by medical students and clinicians seeking up‑to‑date, evidence‑based information on *Tecentriq*.