The Impact of Tumor Immune Microenvironment in EGFR-Mutant Non-Small Cell Lung Cancer on the Efficacy of Osimertinib.

Background

The relationship between the tumor microenvironment, comprising programmed cell death-1 ligand-1 (PD-L1), CD8-positive tumor-infiltrating lymphocytes (CD8+TIL), and FOXP3+TIL, in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and its clinicopathological features and the efficacy of EGFR-tyrosine kinase inhibitors remain poorly understood.

Methods

Patients treated with osimertinib or afatinib as first-line treatment were included. PD-L1 (clone: 22C3) expression was classified as positive or negative; CD8+TIL and FOXP3+TIL expressions were assessed via immunohistochemistry, and categorized as high or low. Thereafter, tumor immune microenvironment (TIME) was categorized into 4 classes according to PD-L1 and CD8+TIL statuses: class 1, positive/high; class 2, negative/low; class 3, positive/low; and class 4, negative/high.

Results

Among the TIME classes, there were no significant correlations with clinicopathological factors. Progression-free survival (PFS) with osimertinib differed according to the TIME classification (median PFS: 7.6 vs. 17.7 vs. 14.8 vs. 34.0 months for classes 1-4, respectively; P = .0019). PFS was significantly shorter in the FOXP3+TIL-high group than in the low group (median PFS: 8.3 vs. 18.1 months, P = .031). Multivariable analysis showed that high FOXP3+TIL status was independently associated with shorter PFS (HR 2.28, P = .019); class 4 TIME was independently associated with longer PFS (HR 0.28, P = .004).

Conclusion

The TIME classification based on PD-L1 and CD8+TIL statuses, as well as FOXP3+TIL status, may help predict the efficacy of osimertinib in EGFR-mutant NSCLC.