Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR-mutated non-small cell lung cancer treated with erlotinib

Abstract

Objectives: The central immune co-inhibitory programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway plays a key role in tumor immune evasion in non-small cell lung cancer (NSCLC). Soluble PD-1 (sPD-1) can be detected in the blood, and preclinical evidence suggests that sPD-1 blocks PD-1/-L1 interaction and improves anti-tumor immunity. The present study compares the concentration of sPD-1 in the serum of advanced NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutation prior to erlotinib treatment and at the time of progression and correlates these results to patient outcome.

Materials and methods: Blood samples from 38 patients with EGFR-mutated advanced NSCLC treated with erlotinib were analyzed for sPD-1 by sandwich ELISA. EGFR mutational status was assessed in circulating tumor DNA (ctDNA) and tumor biopsies.

Results: sPD-1 could be detected in 21% of patients prior to erlotinib treatment, and at disease progression in 37% (p=0.015). An increase in sPD-1 during erlotinib therapy was found in 34%, a decrease in 8% and no change in 58% of patients. An increase in sPD-1 during treatment was associated with prolonged progression-free (adjusted HR 0.32, p=0.013) and overall survival (adjusted HR 0.33, p=0.006), but not associated with the emergence of EGFR T790M mutation in ctDNA at progression or any clinicopathological factors.

Conclusion: Patients with an increase in sPD-1 during erlotinib treatment have a more favorable outcome. Our results emphasize the vast clinical impact of the PD-1/PD-L1 axis, and support the existing preclinical evidence in the bioactive function of sPD-1.

Keywords: EGFR mutation; Erlotinib; Non-small cell lung cancer; Soluble PD-1; Tumor microenvironment.