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What is atezolizumab and how does it work?

Atezolizumab is a humanised immunoglobin G1 monoclonal antibody immune checkpoint inhibitor that binds to programmed death-ligand 1 (PD-L1).

PD-L1 is an immune checkpoint protein that is over-expressed on tumour cells and tumour-infiltrating immune cells. Atezolizumab blocks PD-L1’s interaction with PD-1 and B7-1 receptors on T-cells, which restores anti-tumour T-cell activity.

Atezolizumab in breast cancer

NICE approved the use of atezolizumab with nab-paclitaxel in July 2020, within its marketing authorisation, for treating triple-negative, unresectable, locally advanced or metastatic breast cancer in adults whose tumours express PD-L1 at a level of 1% or more and who have not had previous chemotherapy for metastatic disease.

This approval has been primarily based on data from the IMpassion130 clinical trial, which demonstrated an improvement in median progression-free survival (PFS) with the addition of atezolizumab of 2.5 months in PD-L1-positive triple-negative breast cancer.

Atezolizumab in lung cancer

Atezolizumab is a NICE-approved treatment option for patients with metastatic lung cancer (non-small cell) who have previously been treated with chemotherapy (and targeted therapy if they have an EGFR, ALK, ROS1, MET exon 14, KRAS G12C, RET or BRAF mutation-positive tumour).

This NICE recommendation is based on data from the OAK trial, a phase-three randomised controlled trial in adults with locally advanced or metastatic non-small cell lung cancer, whose disease had progressed during or after one platinum-containing chemotherapy regimen. The results of the primary analysis showed a statistically significant median overall survival gain for treatment with atezolizumab monotherapy (13.8 months; 95% confidence interval (CI) 11.8 to 15.7) compared with docetaxel (9.6 months; 95% CI 8.6 to 11.2).

In addition, atezolizumab plus bevacizumab, carboplatin and paclitaxel (BCP) is recommended by NICE as an option for metastatic non-squamous non-small cell lung cancer in adults who have not had treatment for their metastatic lung cancer before and whose PD-L1 tumour proportion score is between 0%–49% or when targeted therapy for EGFR‑ or ALK‑positive non-small cell cancer has failed.

This approval has been based primarily on data from the IMpower150 trial, which demonstrated a median PFS of 8.2 months for patients treated with atezolizumab with BCP, versus 5.4 months for patients treated with BCP alone.

Atezolizumab is also approved in the treatment of extensive-stage small-cell lung cancer in combination with carboplatin and etoposide chemotherapy. This approval was made due to the results from the IMpower133 study, which showed that the combination of atezolizumab, carboplatin and etoposide chemotherapy led to a statistically significant improvement in median overall survival of 12.3 months (compared with a median overall survival of 10.3 months in the placebo group).

Atezolizumab in urothelial cancer

Atezolizumab is available to adult patients with locally advanced or metastatic urothelial carcinoma who have had platinum-containing chemotherapy. It can also be offered to patients with untreated locally advanced or metastatic urothelial carcinoma if their tumours express PD-L1 at a level of 5% or more when cisplatin-containing chemotherapy is unsuitable.

This approval has been based primarily on the IMvigor130 clinical trial, which demonstrated a median overall survival of 16 months for patients treated with atezolizumab and platinum plus gemcitabine, versus 13.4 months for patients treated with chemotherapy and placebo.

Key messages

  • Atezolizumab is approved by NICE to treat certain types of breast cancer, lung cancer, urothelial carcinoma and hepatocellular carcinoma.
  • Atezolizumab blocks an immune checkpoint protein that is over-expressed on tumour cells and tumour-infiltrating cells.
  • Atezolizumab is often used in combination with chemotherapy drugs.

Resources

For clinicians

References:

Tagged: Therapies, Breast cancer, Lung cancer, Urothelial cancer, Immunotherapy

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  • Last reviewed: 12/12/2023
  • Next review due: 12/12/2025
  • Authors: Dr Nida Pasha
  • Reviewers: Dr Ellen Copson, Dr Amy Frost, Dr Terri McVeigh, Dr Amal Singh