Expression of PD-L1 in Patients with Advanced Non-Small Cell Lung Cancer

Immune Checkpoints and Cancer Treatment

Some tumors are able to evade detection by the body’s immune system by influencing inhibitory immune checkpoints, such as the programmed cell death receptor (PD-1) pathway and its ligand (PD-L1). Treatment with antibodies that block this pathway appears promising for patients with advanced/metastatic NSCLC.

These patients generally have a poor prognosis with a short survival time. Therefore, NSCLC treatment is increasingly personalized, with targeted therapy being chosen based on various defined biomarkers for individual patients. The review authors focused on clinical studies evaluating the relationship between PD-L1 expression, clinicopathological parameters, and prognosis and/or response to therapies targeting the PD-1/PD-L1 pathway.

Findings

Searching the Medline and Embase databases and the proceedings of significant oncology conferences led to the identification of 35 studies that met inclusion criteria and were included in the analysis. PD-L1 expression was most often assessed immunohistochemically, but the methods for determining PD-L1 in tumor tissue varied significantly across studies.

Overall, no association was found between PD-L1 expression and patients’ gender, age, overall health status, or smoking status. PD-L1 expression did not correlate with tumor histology (adenocarcinoma vs. squamous cell carcinoma), differentiation, or mutation status in the EGFR/KRAS/ALK genes.

In several studies, high PD-L1 expression correlated with shorter patient survival compared to low expression. However, most data suggested that patients with high PD-L1 expression are more likely to benefit therapeutically from treatments targeting the PD-1/PD-L1 pathway (nivolumab, pembrolizumab, durvalumab, atezolizumab, avelumab).

Conclusion

Given the variability of methods used to determine PD-L1 expression in tumor tissue samples of NSCLC patients, it would be necessary to establish a standardized validated method for diagnostic determination of PD-L1 expression. Furthermore, it is important to consider that PD-L1 expression in different parts of the tumor and/or tumor sites can be heterogeneous, and expression levels may change over time or in response to the treatment used.

Although available clinical studies indicate that PD-L1 expression is associated with an increased likelihood of response to immune checkpoint inhibitors, high PD-L1 expression does not guarantee that a patient will respond to treatment, and therapeutic response can also be achieved in tumors with low PD-L1 expression.

(este)

Sources:
1. Brody R., Zhang Y., Ballas M. et al. PD-L1 expression in advanced NSCLC: insights into risk stratification and treatment selection from a systematic literature review. Lung Cancer 2017; 112: 200–215, doi: 10.1016/j.lungcan.2017.08.005.
2. Hellmann M., West H. Management of advanced non-small cell lung cancer lacking a driver mutation: Immunotherapy. UpToDate, 2020 Jun 25. Available at: www.uptodate.com/contents/management-of-advanced-non-small-cell-lung-cancer-lacking-a-driver-mutation-immunotherapy#