Association of Pretreatment Neutrophil-to-Eosinophil Ratio with Clinical Outcomes in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab

Shinsuke Suzuki, Tomoe Abe, Tentaro Endo, Haruka Kaya, Takuro Kitabayashi, Yohei Kawasaki, Takechiyo Yamada Department of Otorhinolaryngology & Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, 010-8543, JapanCorrespondence: Shinsuke Suzuki, Department of Otorhinolaryngology & Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, 010-8543, Japan, Tel +81-18-884-6171, Fax +81-18-836-2622, Email suzukis@med.akita-u.ac.jpBackground: There is a need to develop biomarkers for a more efficient use of immune checkpoint inhibitors (ICIs). Recently, it has been reported that peripheral blood components, including eosinophils, may be effective ICI biomarkers. This study was designed to evaluate the prognostic value of eosinophils for measuring the effects of nivolumab on recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).Materials and Methods: The study included 47 patients with R/M HNSCC treated with nivolumab. Eosinophil-related biomarkers, such as absolute eosinophil count (AEC), relative eosinophil count (REC), and neutrophil-to-eosinophil ratio (NER), were measured from the peripheral blood of the patients before nivolumab treatment. For each biomarker, the patients were divided into a high- and a low-value group according to their cutoff values, and these groups were compared.Results: Regarding AEC and REC, no significant improvement in the objective response rate (ORR) was observed between patients with AEC > 0.9 × 103/μL and those with AEC < 0.9 × 103/μL (p = 0.147) and between patients with REC > 2.2% and those with REC < 2.2% (p = 0.110). However, patients with NER < 32 had improved ORR compared with those with NER > 32 (P = 0.0361). Additionally, although patients with AEC > 0.9 × 103/μL, REC > 2.2%, and NER < 32 had longer overall survival (OS) than those with AEC < 0.9 × 103/μL, REC < 2.2%, and NER > 32, only patients with NER < 32 showed prolonged progression-free survival (PFS) compared with those with NER > 32 according to the Log rank test (p = 0.046, 0.027, and 0.035, respectively). Furthermore, the multivariate analysis revealed that baseline NER > 32 (p = 0.027) was an independent prognostic factor for worse OS.Conclusion: A pretreatment feature of low NER (NER < 32) may predict better clinical outcomes in patients with R/M HNSCC treated with nivolumab.Keywords: head and neck cancer, nivolumab, eosinophil, neutrophil-to-eosinophil ratio, recurrent/metastatic head and neck squamous cell carcinoma