Association between soluble immune mediators and outcomes in patients with unresectable stage III non-small cell lung cancer treated with concurrent chemoradiotherapy followed by durvalumab.

Background: The current standard of care for unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT) followed by durvalumab. There are no reliable biomarkers predicting the response to this treatment. We aimed to analyze the relationship between soluble immune mediators and treatment response and to identify biomarkers predicting the treatment response in patients with unresectable stage III NSCLC. Methods: We prospectively enrolled 48 patients diagnosed with stage III NSCLC who underwent thoracic radiotherapy (cohort A). Of these patients, 29 received durvalumab after CCRT (cohort B). Peripheral blood samples were collected before radiotherapy and 6 weeks after durvalumab treatment. To identify soluble immune mediators associated with progression-free survival (PFS) and overall survival (OS), we examined the levels of 83 soluble immune mediators using a bead-based multiplex assay and calculated the concordance index (C-index). Results: At baseline, the high matrix metalloproteinase (MMP)-2 group exhibited the longest PFS and OS in cohort A (C-index: 0.70 and 0.75, respectively), whereas the high IFN-γ group had the worst PFS and OS in cohort B (C-index: 0.75 and 0.71, respectively). Furthermore, patients with greater increases in CXCL9, CXCL10, and CCL23 levels after durvalumab treatment had poor PFS and OS in cohort B (C-index >0.70). Conclusions: Our results suggest that PFS and OS are negatively affected by elevated CXCL9, CXCL10, and CCL23 levels after CCRT followed by durvalumab treatment. These soluble mediators may be useful tools for the clinical management of locally advanced NSCLC treated with PD-L1 therapy after CCRT.