1318P - Neutrophil extracellular traps as a potential predictive marker for treatment with pembrolizumab alone or with chemotherapy as a first-line in patients with metastatic non-small cell lung cancer

Background

In this multicentric retrospective study, we evaluated the correlation between pre-treatment blood neutrophils and neutrophil extracellular traps (NET) in biopsy samples and their predictive value for progression free survival (PFS) in patients with non-small cell lung cancer (NSCLC) receiving immunotherapy alone or in combination with chemotherapy as a first-line treatment.

Methods

Patients with metastatic NSCLC (n=70) were retrospectively analyzed between Apr 2019 and Dec 2020; 80% of the patients received platinum-containing chemotherapy with Pembrolizumab, and 20% – only Pembrolizumab as a first-line treatment. Tissue sections were stained immunohistochemically for Neutrophil elastase (NE) and Histone H3. Both NE and Histone H3 stained tissue areas were calculated manually and determined by Image-J software. We considered the extracellular component that was double-positive for NE and H3 to be NET.

Results

There were no significant relationships between patients` clinicopathological characteristics and detected NETs in the tumor samples. A positive correlation trend was observed between pre-treatment blood neutrophil counts and NET detection in the primary tumours (Rho= 0.22, p=0.07). Patients with a high amount of NET-positive areas (>66^th percentile) had significantly shorter mean PFS, 11.5 months (95% CI: 10.2-13.1) than those with an intermediate/low amount of NET-positive areas, 15.9 months (95% CI: 13.5-18.4) (log-rank test p=0.009). Moreover, in a multivariate Cox regression model, the presence of a high amount of NET-positive areas was an independent predictive factor for shorter PFS, HR 2.5 (95% CI: 1.2-5.1; p=0.012).

Conclusions

High blood neutrophils tend to correlate with a high amount of NET-positive areas in the primary tumours. Excessive NET formation in tumour tissue is a potential negative predictive marker for short PFS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.