Evaluation of Neutrophil to Lymphocyte Ratio in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Treated With a Combination of Cetuximab and Nivolumab in a Phase II Clinical Trial.

Objectives: We report on the biomarker analyses focusing on neutrophil-to-lymphocyte ratios (NLR) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with combined cetuximab and nivolumab.

Methods: Data were obtained from a phase II trial (NCT03370276). Peripheral blood NLR was obtained at baseline (B-NLR) and on-treatment (OT-NLR; 1 mo from treatment initiation). Tumor NLR (T-NLR) was determined by staining of immune cells in primary tumors. Patients were stratified into high (≥median) or low NLR (
Results: While B-NLR did not correlate with survival or responses, low OT-NLR was associated with superior overall survival (OS; P<0.0001), progression-free survival (PFS; P=0.0002), and overall response (P<0.001) compared with high OT-NLR. Multivariable analysis further demonstrated that low OT-NLR was associated with superior OS (HR 0.32, 95% CI, 0.17-0.61) and PFS (HR 0.45, 95% CI, 0.25-0.81). Compared with patients with high OT-NLR, a higher proportion of patients with low OT-NLR had OS≥24 months (P=0.0001). Low OT-NLR was associated with higher baseline PD-L1 combined positive scores (P=0.037). Low pretreatment T-NLR was associated with superior OS and PFS in multivariable analysis and correlated with superior overall response (P=0.011).

Conclusions: Low OT-NLR and pretreatment T-NLR correlated with superior treatment outcomes in patients with R/M HNSCC treated with cetuximab and nivolumab. Further evaluation of T-NLR to improve patient selection and peripheral blood OT-NLR as a dynamic biomarker contributing to clinical benefit assessment given cetuximab and nivolumab is warranted.