Atezolizumab set to change refractory lung cancer treatment

"In the BIRCH trial the PD-L1 antibody atezolizumab showed a remarkable activity in a large number of patients regardless of the line of treatment," said Reck. "The profile of adverse events is in line with reported data from other PD-1/PD-L1 checkpoint inhibitors and overall tolerability looks quite favourable. The efficacy as shown by the response rate was in correlation with PD-L1 expression on tumour and immune cells favouring tumours with high PD-L1 expression."

"In confirmation the randomised POPLAR trial reported a superior overall survival for unselected patients who received atezolizumab as second-line treatment compared to docetaxel," continued Reck. "Again efficacy could be correlated to the PD-L1 expression status with the highest overall survival benefit in patients with TC3 and IC3 (high PD-L1 expressing tumours). The data have to be validated by a large randomised phase III trial, which is ongoing."

Commenting on how atezolizumab compares with current therapies for lung cancer, Reck said: "Atezolizumab is the second checkpoint inhibitor to show a superior efficacy and better tolerability compared to standard second-line chemotherapy in patients with pre-treated non-small cell lung cancer (NSCLC). Therefore it is to be expected that atezolizumab, like other PD-1 and PD-L1 antibodies, will substantially change treatment strategies of patients with refractory lung cancer."

First-line treatment is also promising, said Reck. "First-line treatment with atezolizumab in patients with PD-L1 high expressing tumours or the combination of atezolizumab with platinum-based chemotherapy remains an attractive option and is currently being investigated in large randomised phase III trials. Furthermore, activity is also seen in different tumours like small cell lung cancer (SCLC) and mesothelioma and will be explored in upcoming trials."

It is expected that pre-treatment of patients will change dramatically based on the findings from POPLAR and BIRCH and other reported data with the PD-1 antibody nivolumab, which was recently approved by the European Medicines Agency (EMA) for the treatment of patients with refractory squamous cell NSCLC.

"In particular, the option for long-lasting responses and stabilisation in combination with an attractive tolerability profile will impact clinical practice," said Reck. "Whether patients should be selected using a biomarker strategy still needs to be determined and remains a significant challenge based on the multiple different companion diagnostics that are in use for the particular agents. Depending on the results of ongoing trials front-line treatment with a checkpoint inhibitor in selected patients could be an interesting option."