Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients

Takashi Matsuki; Isaku Okamoto; Chihiro Fushimi; Michi Sawabe; Daisuke Kawakita; Hiroki Sato; Kiyoaki Tsukahara; Takahito Kondo; Takuro Okada; Yuichiro Tada; Kouki Miura; Go Omura; Taku Yamashita

doi:10.1002/cam4.3124

Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients

Cancer Med. 2020 Jul;9(14):5015-5024. doi: 10.1002/cam4.3124. Epub 2020 May 22.

Authors

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
² Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University School of Medicine, Tokyo, Japan.
³ Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
⁵ Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan.
⁶ Department of Head and Neck Oncology, National Cancer Center Hospital, Tokyo, Japan.

Abstract

Background: There is increasing evidence that immunotherapy with nivolumab, an anti-programmed death 1 monoclonal antibody, is effective in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the predictive role of hematological inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and the modified Glasgow prognostic score (mGPS) in patients with R/M SCCHN treated with nivolumab remains unclear.

Methods: We conducted a multi-institutional cohort study to evaluate the impact of pretreatment NLR and mGPS on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with nivolumab in Japan. From 2012 to 2013, 102 patients were eligible, of whom 88 were finally included in the analysis. mGPS was calculated as follows: mGPS of 0, C-reactive protein (CRP) ≤1.0 mg/dL; 1, CRP > 1.0 mg/dL; and 2, CRP > 1.0 mg/dL and albumin < 3.5 mg/dL. Optimal cutoff point of dichotomized NLR was calculated using the area under the receiver operating characteristic curve (AUROC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models adjusted by potential confounders.

Results: Higher NLR was significantly associated with worse survival (1-year OS: 45.3% vs 16.3%, log-rank P-value < .001, adjusted HR: 4.40 (95% CIs: 1.78-10.88); one-year PFS: 39.1% vs 9.0%, P-value = .001, adjusted HR: 3.37 (95% CI: 1.64-6.92)). In addition, high mGPS (=2) was significantly associated with worse survival compared to low mGPS (=0) (1-year OS: 37.4% vs 26.1%, P-value = .004, adjusted HR: 4.20 (95% CI:1.54-11.49); 1-year PFS: 41.5% vs 24.8%, P-value = .007, adjusted HR: 2.01 (95% CI: 0.87-4.68)). These associations were consistent with subgroup analyses stratified by potential confounders.

Conclusions: Pretreatment NLR and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with nivolumab.

Keywords: biomarkers; head and neck cancer.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological / pharmacology
Antineoplastic Agents, Immunological / therapeutic use*
Female
Humans
Male
Middle Aged
Neoplasm Metastasis
Nivolumab / pharmacology
Nivolumab / therapeutic use*
Prognosis
Squamous Cell Carcinoma of Head and Neck / drug therapy*
Squamous Cell Carcinoma of Head and Neck / pathology
Young Adult

Substances

Antineoplastic Agents, Immunological
Nivolumab