Atezolizumab

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.

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 (Schmid and others, 2018), 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 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- or ALK‑positive tumour).

This NICE recommendation is based on data from the OAK trial, a phase 3 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) (Rittmeyer and others, 2017).

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 IMpower150 trial (Socinski and others, 2018), which demonstrated that a median PFS of 8.2 months when treated with atezolizumab with BCP, versus 5.4 months for patients treated with BCP alone.

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 (OS) of 16 months when treated with atezolizumab and platinum plus gemcitabine, versus 13.4 months for patients treated with chemotherapy and placebo (Galsky and others, 2020).

For clinicians

• NICE: Atezolizumab in breast cancer
• NICE: Atezolizumab in lung cancer – recommendations
• NICE: Atezolizumab in lung cancer – atezolizumab plus BCP
• NICE: Atezolizumab in urothelial cancer

References:

• Galsky MD, Arranz Arija JA, Bamias A and others. ‘Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial’. The Lancet 16 May 2020: volume 395, issue 10,236, pages 1,547-57. doi: 10.1016/S0140-6736(20)30230-0
• Rittmeyer A, Barlesi F, Waterkamp D and others. ‘Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial’. The Lancet 21 Jan 2017: volume 389, issue 10,066, pages 255-65. doi: 10.1016/S0140-6736(16)32517-X. Erratum in: The Lancet 8 Apr 2017: volume 389, issue 10,077, page e5. doi: 10.1016/S0140-6736(17)30904-2
• Schmid P, Adams S, Rugo H and others. ‘Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer’. The New England Journal of Medicine 29 Nov 2018: volume 379, issue 22, pages 2,108-21. doi: 10.1056/NEJMoa1809615
• Socinski MA, Jotte RM, Cappuzzo F and others.  ‘Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC’. The New England Journal of Medicine 14 Jun 2018: volume 378, issue 24, pages 2,288-2,301. doi: 10.1056/NEJMoa1716948