Abstract 3200: Association between inflammatory gene expression signatures in blood or tumor samples and response to nivolumab in patients with SCCHN
Authors: Li Jun , Szabo Peter M. , Chasalow Scott D. , Chang Han , Apfel Abraham , Roberts Mustimbo , Neely Jaclyn 
Published: September 2020

Abstract
Background: Tumor inflammation has been associated with response to nivolumab (NIVO) in patients with cancer. In patients with squamous cell carcinoma of the head and neck (SCCHN), inflammation in tumor tissue samples can be assessed with inflammatory gene expression signature scores determined by gene expression profiling (GEP); however, tissue availability may be limited. We evaluated the association between inflammatory signature scores, assessed by GEP using blood or tumor samples, and response to NIVO.
Methods: In post-hoc analyses, GEP was performed by RNA-seq on pre- (D1) and on-treatment (D43) whole blood samples and pretreatment tumor samples from patients with SCCHN treated with NIVO or investigator's choice (IC) therapy (CheckMate 141; NCT02105636). Scores for blood and tumor samples were calculated for multiple published tissue-derived inflammation signatures, and association with progression-free survival (PFS), overall survival (OS), and objective response (OR) was evaluated.
Results: GEP was evaluable in 278 D1 (188 NIVO, 90 IC) and 186 D43 (129 NIVO, 57 IC) blood samples. For a 13-gene inflammation signature, signature scores from pretreatment tumor and matched blood samples were correlated (r = 0.33). For D1 and D43 blood samples, both OS and PFS were positively associated with signature scores in at least 1 of the treatment groups, and treatment benefit with NIVO vs IC increased with increasing score. OR was positively associated with signature scores for D1 and D43 samples, especially for NIVO-treated patients (Table). Results were highly correlated between multiple inflammation signatures.
TableHazard ratio (95% confidence interval)aPFSOSBlood samplesD1D43D1D43NIVO vs ICLow inflammation scoreb1.1 (0.8–1.5)1.2 (0.8–1.8)0.9 (0.7–1.3)0.9 (0.6–1.3)High inflammation scorec0.8 (0.6–1.2)0.7 (0.4–1.1)0.7 (0.5–1.0)0.5 (0.3–0.8)High vs low inflammation scoredNIVO0.6 (0.5–0.8)0.6 (0.4–0.8)0.5 (0.4–0.6)0.5 (0.3–0.7)IC0.9 (0.6–1.2)1.1 (0.7–1.6)0.6 (0.5–0.9)0.8 (0.6–1.2)NIVO vs IC0.7 (0.5–1.1)0.6 (0.3–0.9)0.7 (0.5–1.1)0.6 (0.4–0.9)Area under the receiver operating characteristic curve for OR, %Blood samplesD1D43NIVO60.765.3IC52.655.7aCox proportional-hazards model.b25th inflammation score percentile.c75th inflammation score percentile.d75th vs 25th inflammation score percentile.D1, pretreatment samples; D43, on-treatment samples; IC, investigator's choice of therapy; NIVO, nivolumab; OS, overall survival; PFS, progression-free survival.
Conclusion: Inflammation signature scores correlated between SCCHN tumor and matched blood samples and were associated with outcomes, especially for NIVO treatment. Further study of inflammation signatures using blood-based GEP is warranted to further assess tumor inflammation and its association with response to NIVO in SCCHN.
Citation Format: Jun Li, Peter M. Szabo, Scott D. Chasalow, Han Chang, Abraham Apfel, Mustimbo Roberts, Jaclyn Neely. Association between inflammatory gene expression signatures in blood or tumor samples and response to nivolumab in patients with SCCHN [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3200.