Tecentriq (Atezolizumab) Prescribing Information and Clinical Use
This document provides comprehensive prescribing information for Tecentriq (atezolizumab), a humanized immunoglobulin G1 (IgG1) monoclonal antibody used in cancer therapy.
1. Description
Tecentriq is an antineoplastic agent. It is available in two formulations: an intravenous (IV) concentrate for solution for infusion and a subcutaneous (SC) solution for injection. The active ingredient is atezolizumab. Tecentriq SC also contains recombinant human hyaluronidase (rHuPH20).
2. Therapeutic Indications
Tecentriq is indicated for the treatment of various cancers, including:
- Early-stage Non-Small Cell Lung Cancer (NSCLC): As adjuvant treatment following complete resection for patients with Stage II to IIIA NSCLC whose tumors have PD-L1 expression (≥50% tumor cells or ≥10% tumor-infiltrating immune cells) and whose disease has not progressed following platinum-based adjuvant chemotherapy.
- Metastatic Non-Small Cell Lung Cancer (NSCLC):
- In combination with Avastin, paclitaxel, and carboplatin for treatment-naïve patients with metastatic non-squamous NSCLC.
- As monotherapy for patients with disease progression during or following platinum-containing chemotherapy, provided EGFR or ALK genomic tumor aberrations have been addressed.
- In combination with nab-paclitaxel and carboplatin for first-line treatment of metastatic non-squamous NSCLC without EGFR or ALK genomic tumor aberrations.
- As monotherapy for first-line treatment of metastatic NSCLC with PD-L1 expression (≥50% tumor cells or ≥10% tumor-infiltrating immune cells) and without EGFR or ALK genomic tumor aberrations.
- As monotherapy for first-line treatment of adult patients with NSCLC ineligible for platinum-based chemotherapy, who have locally advanced, unresectable NSCLC not amenable for definitive chemoradiotherapy, or metastatic NSCLC.
- Small Cell Lung Cancer (SCLC): In combination with carboplatin and etoposide for first-line treatment of extensive-stage SCLC.
- Triple-Negative Breast Cancer (TNBC): In combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic TNBC whose tumors have PD-L1 expression (≥1% on tumor-infiltrating immune cells) and have not received prior chemotherapy for metastatic disease.
- Hepatocellular Carcinoma (HCC): In combination with Avastin for patients with unresectable HCC who have not received prior systemic therapy.
3. Dosage and Administration
Tecentriq must be administered under the supervision of a qualified healthcare professional. It is crucial to ensure the correct formulation (IV or SC) is administered.
Tecentriq IV: Administered as an intravenous infusion, initially over 60 minutes, which may be reduced to 30 minutes for subsequent infusions if tolerated. Do not administer as an IV push or bolus.
Tecentriq SC: Administered as a subcutaneous injection, typically 15 mL in the thigh over approximately 7 minutes. Use of a SC infusion set (e.g., winged/butterfly) is recommended. Injection sites should be alternated.
Patient Selection: For specific indications, patients are selected based on PD-L1 tumor expression confirmed by a validated test.
Recommended Dose and Schedule
Refer to the tables below for specific dosing recommendations for monotherapy and combination therapies.
| Indication | Recommended Dose and Schedule | Duration of Treatment |
|---|---|---|
| 1L and 2L NSCLC | Tecentriq IV: 840 mg every 2 weeks OR 1200 mg every 3 weeks OR 1680 mg every 4 weeks | Until loss of clinical benefit or unacceptable toxicity |
| Early-stage NSCLC | Tecentriq SC: 1875 mg every 3 weeks | For 1 year unless disease recurrence or unacceptable toxicity |
| Indication | Recommended Dose and Schedule | Duration of Treatment |
|---|---|---|
| 1L non-squamous metastatic NSCLC (with Avastin, paclitaxel, carboplatin) | Tecentriq IV: 840 mg every 2 weeks OR 1200 mg every 3 weeks OR 1680 mg every 4 weeks (Induction: 4-6 cycles) | Until loss of clinical benefit or unacceptable toxicity |
| 1L non-squamous metastatic NSCLC (with nab-paclitaxel, carboplatin) | Tecentriq SC: 1875 mg every 3 weeks | |
| 1L ES-SCLC (with carboplatin, etoposide) | Tecentriq IV: 840 mg every 2 weeks OR 1200 mg every 3 weeks OR 1680 mg every 4 weeks | Until disease progression or unacceptable toxicity |
| 1L unresectable locally advanced or metastatic TNBC (with nab-paclitaxel) | Tecentriq SC: 1875 mg every 3 weeks | |
| HCC (with Avastin) | Tecentriq IV: 840 mg every 2 weeks OR 1200 mg every 3 weeks OR 1680 mg every 4 weeks | Until loss of clinical benefit or unacceptable toxicity |
| Tecentriq SC: 1875 mg every 3 weeks |
Delayed or Missed Doses: If a dose is missed, administer it as soon as possible and adjust the schedule accordingly.
Dose Modifications for Immune-Mediated Adverse Reactions: Specific recommendations for managing adverse reactions like pneumonitis, hepatitis, colitis, and endocrinopathies are provided, often involving withholding or permanently discontinuing Tecentriq and initiating corticosteroid therapy.
4. Warnings and Precautions
Tecentriq can cause immune-mediated adverse reactions, which may be severe or fatal. Patients must be monitored for clinical signs and symptoms of these reactions, including:
- Immune-mediated Pneumonitis: Monitor for signs and symptoms.
- Immune-mediated Hepatitis: Monitor liver function tests (AST, ALT, bilirubin).
- Immune-mediated Colitis: Monitor for diarrhea or colitis.
- Immune-mediated Endocrinopathies: Monitor thyroid function, adrenal function, and glucose levels.
- Immune-mediated Neuropathies: Monitor for symptoms of motor and sensory neuropathy.
- Immune-mediated Myelitis: Monitor for signs suggestive of myelitis.
- Immune-mediated Pancreatitis: Monitor for signs of acute pancreatitis.
- Immune-mediated Myocarditis: Monitor for signs and symptoms.
- Immune-mediated Myositis: Monitor for signs and symptoms.
- Immune-mediated Nephritis: Monitor for changes in renal function.
- Immune-mediated Severe Cutaneous Adverse Reactions (SCARs): Monitor for severe skin reactions.
- Immune-mediated Pericardial Disorders: Monitor for signs and symptoms.
Other potential adverse reactions include haemolytic anaemia and aplastic anaemia. Caution is advised in patients with autoimmune diseases.
Embryofetal Toxicity: Tecentriq may cause fetal harm. Pregnant women should be advised of the potential risk.
Infection: Severe infections have been observed. Monitor for signs and symptoms of infection.
Ocular Inflammatory Toxicity: Monitor for ocular inflammatory toxicity.
Ability to Drive and Use Machines: No studies have been performed.
5. Use in Special Populations
- Reproductive Potential: Female patients of childbearing potential should use effective contraception during and for 5 months after treatment.
- Pregnancy: Not recommended unless the potential benefit outweighs the risk to the fetus.
- Lactation: Decision to breastfeed or discontinue Tecentriq must be made carefully.
- Pediatric Use: Safety and efficacy not established in patients under 18 years.
- Geriatric Use: No overall differences in safety or efficacy observed in patients ≥ 65 years.
- Renal Impairment: No dose adjustment required.
- Hepatic Impairment: No dose adjustment required for mild or moderate impairment. Data for severe impairment is limited.
6. Undesirable Effects
The safety profile of Tecentriq has been evaluated in clinical trials and postmarketing surveillance. Adverse drug reactions (ADRs) are categorized by frequency.
Common ADRs (Tecentriq Monotherapy): Fatigue, cough, dyspnea, pyrexia, rash, diarrhea, nausea, AST increased, ALT increased, arthralgia, hypothyroidism, decreased appetite, urinary tract infection.
Immune-mediated ADRs (Monotherapy): Hypothyroidism, hyperthyroidism, adrenal insufficiency, pneumonitis, hepatitis, colitis, dermatitis, nephritis, and others have been reported. Management often involves dose modification or discontinuation.
ADRs in Combination Therapy: Additional ADRs are observed when used in combination, including anemia, neutropenia, lymphopenia, thrombocytopenia, leukopenia, peripheral neuropathy, and hypertension.
Detailed tables of ADRs from clinical trials and postmarketing surveillance are available, listing frequencies and severity.
7. Clinical / Efficacy Studies
Tecentriq has been evaluated in numerous clinical trials across various cancer types. Key studies and their findings include:
- IMpower010 (Early-stage NSCLC): Demonstrated improved disease-free survival (DFS) in patients with PD-L1 expression ≥1% TC.
- IMpower150 (Metastatic NSCLC): Showed improved overall survival (OS) and progression-free survival (PFS) when Tecentriq was combined with Avastin, paclitaxel, and carboplatin compared to chemotherapy alone.
- IMpower130 (Metastatic NSCLC): Demonstrated improved OS and PFS with Tecentriq plus nab-paclitaxel and carboplatin versus chemotherapy in treatment-naïve patients.
- IMpower110 (Metastatic NSCLC): Showed improved OS in patients with PD-L1 expression ≥1% TC or ≥1% IC, particularly in those with high PD-L1 expression.
- MO29872 (IPSOS) (NSCLC ineligible for platinum-based chemotherapy): Demonstrated improved OS compared to single-agent chemotherapy.
- IMpower133 (ES-SCLC): Showed improved OS and PFS when Tecentriq was combined with carboplatin and etoposide.
- IMpassion130 (TNBC): Demonstrated improved PFS and OS when Tecentriq was combined with nab-paclitaxel in patients with PD-L1 expression ≥1%.
- IMbrave150 (HCC): Showed significant improvements in OS and PFS when Tecentriq was combined with Avastin compared to sorafenib.
- IMscin001 (NSCLC): Evaluated the efficacy and safety of Tecentriq SC versus IV, demonstrating comparable efficacy and patient preference for SC administration.
Patient-reported outcomes generally showed maintained quality of life and physical functioning across studies.
8. Pharmacokinetic Properties
The pharmacokinetics of atezolizumab have been characterized for both IV and SC administration. Key findings include:
- Absorption: For Tecentriq SC, absolute bioavailability is approximately 72%.
- Distribution: Central compartment volume of distribution is approximately 3.28 L.
- Metabolism: Antibodies are cleared principally by catabolism.
- Elimination: Typical terminal elimination half-life is approximately 27 days.
- Special Populations: Age, body weight, gender, renal impairment, and mild/moderate hepatic impairment generally do not have a clinically relevant effect on pharmacokinetics.
9. Nonclinical Safety
No carcinogenicity or genotoxicity studies have been conducted with Tecentriq. Animal studies suggest potential for embryo-fetal toxicity, and Tecentriq may impair fertility in females.
10. Pharmaceutical Particulars
Storage
Tecentriq IV and SC vials should be stored at 2°C-8°C and protected from light. Do not freeze or shake. Diluted solutions for infusion should be used promptly.
Special Instructions for Use, Handling and Disposal
Preparation should be done by a healthcare professional using aseptic technique. Specific instructions are provided for dilution of Tecentriq IV and preparation of Tecentriq SC syringes. Unused medicines should be disposed of responsibly.
Packs
Tecentriq is available in vials of various strengths for IV and SC administration.
For more information, please visit www.roche.com.sg/pharma/tecentriq.
