The Scottish Inflammatory Prognostic Score (SIPS) predicts survival with first-line EGFR inhibitors in non-small cell lung cancer


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Amanda Swan1, Kirsten Cumming1, Tze-En Ding1, Colin Barrie1, Kirsty MacLennan1, Sorcha Campbell1, Tamasin Evans1, Aisha Tufail1, Melanie Mackean1, Iain Phillips1, Mark Stares2
1Edinburgh Cancer Centre, 2University of Edinburgh

Abstract

Background

Approximately 10-15% of patients with metastatic non-small cell lung cancer harbour epidermal growth factor receptor (EGFR) activating mutations. For these patients EGFR-tyrosine kinase inhibitors (TKI) are considered standard first-line treatment. Although molecular biomarkers may predict sensitivity to specific treatments broader prognostic biomarkers for these treatments are lacking. We evaluated the prognostic significance of a novel biomarker of systemic inflammation, the Scottish Inflammatory Prognostic Score (SIPS) in patients receiving first-line EGFR-TKI for NSCLC.

Method

All patients treated with first-line EGFR-TKI for advanced NSCLC at a regional Scottish cancer centres were identified. Neutrophil count and albumin within 14 days prior to starting therapy were used to calculate SIPS - 1 point each for albumin <35g/L and neutrophil >7.5X109/L to give a 3-tier categorical score. The relationship between SIP and progression-free survival (PFS) and overall survival (OS) was examined.

Results

Data were available for 132 patients. Median age was 67 (interquartile range 58-75) and 68% were female. 54 (41%), 62 (47%) and 16 (12%) of patients received first-line afatinib, erlotinib or osimertinib therapy respectively. Median PFS was 11.5 months. At censoring 16 (12%) of patients had no progressive disease, for whom minimum and median follow-up was 5.1 months and 11.9 months respectively. Median OS was 17.6 months. At censoring 40 (30%) of patients were alive, for whom minimum and median follow-up was 6.2 months and 16.8. months respectively. 55 (42%), 49 (37%) and 28 (21%) of patients were SIPS0, 1 and 2 respectively. SIPS was predictive of PFS (HR1.70 95%CI 1.31-2.20 (p<0.001)) and OS (HR1.79 95%CI 1.35-3.38 (p<0.001)). SIPS stratified PFS from 6.2 months (SIPS2) to 11.9 months (SIPS1) to 14.3 months (SIPS0) (p<0.001) and OS from 7.7 months (SIPS2), to 18.7 (SIPS1) to 25.8 (SIPS0) months (p<0.001).

Conclusion

SIPS, a novel biomarker of systemic inflammation combining neutrophil count and albumin, predicts survival in patients with NSCLC receiving first-line EGFR-TKI. In particular, this simple score identifies a small, but significant group of patients with SIPS2 who derive limited clinical benefit from these treatments. Further work is needed to define the risks and benefits of this approach.

Impact statement

SIPS predicts survival in patients with NSCLC receiving first line EGFR-TKI.