Are immune checkpoint inhibitors effective for non-small-cell lung cancer spread to the brain or liver?

This study was carried out to look at the effectiveness of immune checkpoint inhibitors (ICI) in non-small cell cancer (NSCLC) patients with different sites of cancer spread. The authors found that ICIs could significantly improve the overall survival (OS) of patients NSCLC spread to the brain or liver compared to conventional treatments.

Lung cancer is one of the leading causes of cancer-related deaths in the world. NSCLC accounts for 85% of all cases of lung cancer in the United States. Lung cancer is known to spread (metastasize) to different parts of the body with the brain and liver being common sites of spread. 

ICIs such as pembrolizumab (Keytruda), nivolumab (Opdivo), or atezolizumab (Tecentriq) among others act on the immune system. Checkpoint proteins such as PD-1, PD-L1, or CTLA-1 can be found on NSCLC cells and prevent the immune system to detect and kill these cells. ICIs block these proteins and therefore allow the immune system to attack cancer cells. ICIs have improved the outcomes of patients with NSCLC. However, whether patients with NSCLC that has spread to different places gain more benefits from ICIs compared to conventional treatments remains unknown. 

The authors looked at 8 studies about ICIs in patients with metastatic NSCLC. Overall, there were 988 patients. 259 of these patients had lung cancer spread to the brain. 729 of these patients had lung cancer spread to the liver.  

For patients with lung cancer spread to the brain, the use of ICIs resulted in a 43% better overall survival (OS) compared to chemotherapy. Patients treated with PD-1 inhibitors such as pembrolizumab or nivolumab had a 57% higher OS compared to chemotherapy. Patients with brain metastases had the most benefit in OS (by 59%) when ICIs were combined with chemotherapy. 

In patients with lung cancer spread to the liver, OS was higher in the ICI groups by 28% when compared to patients not taking ICIs. These patients also had a higher OS benefit (by 34%) when treated with PD-1 inhibitors. Patients with liver metastases had significantly higher OS with both single ICI therapy (by 32%) and ICI combined with chemotherapy and targeted therapy against VEGF such as bevacizumab (Avastin; by 48%).

The patients with NSCLC and liver metastases, the survival without cancer worsening was 35% better with ICI treatment compared to other treatments. This benefit was seen for all types of ICIs alone or in any combination. 

The authors concluded that ICIs significantly improved the outcomes of patients with NSCLC spread to the brain or liver. 

The number of studies analyzed was small. Also, many studies do not report data on specific metastatic sites. This might influence the results. More studies are needed.