Atezolizumab - Precautions and toxicity | Effects
Atezolizumab is a novel drug approved by FDA for the treatment of advanced or metastatic urothelial carcinoma in patients who didn't respond to the platinum therapy. It works by blocking the programmed death ligand 1, also known as PD-L1.
PD-L1 is a part of cancer immunity cycle which is a seven-step process that helps your body to fight and kill cancer cells. PD-L1 is expressed on the tumor cells and it binds on PD-1 receptors which are found on cytotoxic T-cells (cytotoxic T-cells are part of our immune system and they kill cancer cells). When PD-L1 binds to the PD-1 receptor that causes suppression of a cytotoxic T-cells activity and thus prevent killing of tumor. By preventing PD-L1 binding to the PD-1, Atezolizumab effectively lead to the tumor apoptosis - death of cancer cells.
But, not all the tumors have the same expression of PD-L1 on the cancer cell. That's why, Atezolizumab is more effective against those tumors with higher expression of PD-L1 than in those with lower expression.
Expression of PD-L1 on tumor cells can easily be determined with simple diagnostic tests and is certainly recommended prior Atezolizumab therapy.
Recently, single-arm, multicentre, phase 2 trial was conducted and 26% of patients taking Atezolizumab had complete response (beyond three years), while 15% of patients had partial response. 1 This is a high response rate, considering the fact that most of the patients who didn't respond to the platinum chemotherapy do not survive longer than one year after the treatment. Also, historical data show that average response rate with other drugs is only 10%. Atezolizumab gives hope for many patients with advanced or metastatic urothelial carcinoma.
Picture 1: Atezolizumab in Cancer Immunity Cycle
Precautions and Atezolizumab toxicity
According to the FDA, there are no contraindications.
Unlike other anticancer drugs, Atezolizumab did not cause neutropenia as an adverse effect. Most commonly reported side effect was fatigue (30% of patients had experienced this adverse effect). Most of the adverse effects were mild to moderate and did not require treatment discontinuation.
Renal toxicity was not observed.
Mild increase in the levels of liver enzymes was observed. According to the FDA, immune-mediated liver inflammation can occur while you're on the Atezolizumab treatment. In study conducted on 523 patients, one patient died from immune-mediated liver inflammation, therefore monitoring of liver function during the treatment is recommended.
Other adverse effects reported during the phase 2 trial include:
- Nausea (14%)
- Decreased appetite (12%)
- Itching (10%)
- Increased body temperature (9%)
- Diarrhea (8%)
- Urinary tract infections (7.1%)
- Skin rash (7%)
- Joint pain (7%)
- Vomiting (6%)
- Shortness of breath (3%)
- Anemia (3%)
- Increased levels of liver enzymes (3%)
- Thyroid disorders (2.5%)
- Inflammatory pneumonitis (2%) characterized by difficulty breathing and dry cough. Pneumonitis was the most serious adverse effect reported in the study.
- Low blood pressure (2%)
- High blood pressure (1%)
- Inflammation of the colon (1%)
- Adrenal insufficiency (0.4%)
- Inflammation of the pituitary gland (0.2%)
It is known that drugs used for the treatment of cancer are the most toxic ones, but Atezolizumab did not shown that level of toxicity so far.
Atezolizumab, pregnancy and breastfeeding
Since Atezolizumab is novel drug, currently there are no studies on its use during pregnancy or breastfeeding. Considering its mechanism of action (inhibition of PD-1/PD-L1 pathway) it is expected that this drug will cause immune-related rejection of the embryo which will cause its death. It should be used during pregnancy if the benefits to the mother outweigh the risk to the fetus.
Avoid breastfeeding while you're being treated with Atezolizumab.
Recommended dosage is 1200 mg intravenously as a slow intravenous infusion (over one hour) every 21 days.
Currently, there are no in vivo or in vitro studies interaction studies.
- Rosenberg EJ, Hoffman-Censits J. Powles T and others. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016. 387: 1909-20.