The U.S. Food and Drug Administration (FDA) first approved atezolizumab (Tecentriq®) in 2016, but it received additional approvals when used in combination treatments for locally advanced or metastatic triple negative breast cancer (TNBC) and small cell lung cancer (SCLC) in March 2019.
Atezolizumab’s new indication in combination with protein-bound paclitaxel for TNBC in patients who have not received prior chemotherapy for metastatic disease was evaluated in IMpassion130, a multicenter, international, randomized, double-blinded placebo-controlled trial. And its new use with carboplatin and etoposide in the treatment of SCLC was evaluated in IMpower133, a randomized, multicenter, double-blind, placebo-controlled trial.
Immunotherapy/programmed death-ligand 1 (PD-L1) blocking monoclonal antibody (checkpoint inhibitor)
FDA approved two new indication for atezolizumab in March 2019: TNBC and SCLC. It was previously approved for urothelial carcinoma and non-small cell lung cancer.
TNBC: Atezolizumab is indicated for use in combination with protein-bound paclitaxel for the treatment of adult patients with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells of any intensity covering at least 1% of the tumor area), as determined by an FDA-approved test. The indication was given accelerated approval based on progression-free survival.
SCLC: Atezolizumab is indicated for use in combination with carboplatin and etoposide for the first-line treatment of adult patients with extensive-stage SCLC.
Dosing and Administration
TNBC: 840 mg via IV over 60 minutes, followed by 100 mg/m2 protein-bound paclitaxel. For each 28-day cycle, atezolizumab is administered on days 1 and 15 and protein-bound paclitaxel is administered on days 1, 8, and 15.
SCLC: 1,200 mg IV over 60 minutes every three weeks. Administer atezolizumab prior to chemotherapy when given the same day.
Additional administration instructions:
- If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.
- Do not co-administer other drugs through the same IV line.
- Do not administer as an IV push or bolus.
The following reactions are for the combination treatments with the two new indications. Additional adverse reactions when used as a single agent can be found in the package insert.
TNBC: The most common adverse reactions (reported in at least 20% of patients) with atezoluzimab in combination with protein-bound paclitaxel are alopecia, peripheral neuropathies, fatigue, nausea, diarrhea, anemia, constipation, cough, headache, neutropenia, vomiting, and decreased appetite.
SCLC: Most common adverse reactions (reported in at least 20% of patients) with atezoluzimab in combination with other antineoplastic drugs are fatigue/asthenia, nausea, alopecia, constipation, diarrhea, and decreased appetite.
Monitor for immune-mediated adverse effects, including pneumonitis, hepatitis, colitis, and endocrinopathies (hypophysitis, changes in thyroid function, adrenal insufficiency, and hyperglycemia). Additionally, monitor for infection. The therapy may need to be withheld or discontinued permanently based on the severity of adverse effects.
Infusion reaction can occur, and infusion should be interrupted, slowed, or permanently discontinued based on the severity of the reaction (see package insert for dosage modifications).
Atezolizumab can cause fetal harm; advise women of reproductive potential of the possible risk to a fetus and to use effective contraception during treatment and five months following the last dose. Women of childbearing potential should have a pregnancy test before beginning treatment. In addition, women receiving atezolizumab should not breastfeed their children during treatment and for five months after their last dose.
Drug-Drug and Drug-Food Interactions
The drug interaction potential of atezolizumab is unknown.
- Include information about all adverse reactions, especially immune-related, as well as monitoring and management instructions for those adverse reactions.
- Provide instructions on when and who to notify if an adverse reaction occurs.
- If patients are women of childbearing age, include information on using effective contraception during treatment and five months following their last dose and to avoid breastfeeding their children during treatment and five months following their last dose.
No overall differences in safety or effectiveness were observed between patients aged 65 years or older and younger patients.
Atezolizumab is considered a hazardous drug because it can cause embryo-fetal toxicity and may impair fertility in females of reproductive potential.
Patient Assistance Programs
Patient assistance may be available at Tecentriq's® website.