Do single or combined immune checkpoint inhibitors improve outcomes in patients with advanced non-small cell lung cancer?

This article looked at the effectiveness and safety of first-line immune checkpoint inhibitors (ICIs) alone or as a combination compared to platinum-based chemotherapy (PBC) for advanced non-small cell lung cancer (NSCLC). The authors found that ICI therapy may improve the survival of these patients while having reduced side effects.

NSCLC is responsible for around 85% of lung cancer diagnoses. Despite current treatment options improving survival rates, advanced NSCLC can be difficult to treat.

PD-L1 is a protein (checkpoint) that can be found in high numbers on cancer cells. These proteins can stop the immune system from killing cancerous cells. ICIs are immunotherapies that block checkpoint proteins on cancer cells that can weaken the immune response towards the cancer. Therefore, ICIs allow the immune cells to better detect and kill cancer cells. ICIs have been shown to be effective in improving the outcomes of patients with advanced NSCLC. However, whether ICIs alone or combined are better than first-time standard platinum-based chemotherapy (PBC) in patients with advanced NSCLC is still unknown. 

The authors analyzed the results of 7 clinical trials for this article. Overall, 5893 patients with advanced NSCLC were included. Patients were treated with one type of ICI, a combination of 2 ICIs, or standard PBC with or without targeted therapy bevacizumab (Avastin). ICIs included nivolumab (Opdivo), pembrolizumab (Keytruda), durvalumab (Imfinzi), atezolizumab (Tecentriq), and cemiplimab (Libtayo).

In trials that used a single ICI as treatment, patients with a high PD-L1 rate (50% or more cancer cells expressing PD-L1) experienced a 32% higher overall survival and survival without cancer worsening compared to patients taking PBC. Patients with a high PD-L1 level were also 40% more likely to respond to ICI single-drug therapy compared to PBC.

Side effects were 59% less common in the single ICI group compared to the PBC group. Also, patients treated with single ICI therapy were 51% more likely to have a better quality of life after 15 weeks. 

In trials that used 2 ICIs as a combination, patients with a high PD-L1 rate were 28% more likely to survive when compared to PCB. Severe side effects were not significantly different between PBC and 2 ICIs combination.

The authors found that ICI therapy might improve the outcomes of patients with advanced NSCLC compared to standard chemotherapy, with fewer side effects.