Clinical Variables Associated with Survival and Treatment Response in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Despite recent changes in treatment for unresectable recurrent or metastatic head and neck squamous cell carcinoma (R/M HNC) survival remains poor. Clinical trials fail to capture the diversity of patients and spectrum of disease presentation. This study examines clinically pertinent prognostic variables, efficacy of treatment regimens, and factors associated with response to first line treatment at a high-volume NCI cancer center. <h3>Materials/Methods</h3> A retrospective analysis of patients diagnosed with R/M HNC between 1998- 2018 was performed (n=477). Bivariate and multivariate Cox regression analysis identified independent predictors of survival. Covariates included HPV status, primary site, smoking, ECOG performance status, Charleson comorbidity index, organ dysfunction, BMI, neutrophil/lymphocyte ratio (NLR), tumor volume, platinum sensitivity, location of metastases, and disease-free interval (DFI, time from definitive therapy to R/M diagnosis). Variables with significant bivariate comparisons and no collinearity were included in multivariate analysis. Given retrospective nature of the database, time on treatment was used as a surrogate marker of treatment response. We examined clinical variables associated with time on treatment and patterns of metastasis using T tests and Chi square analyses. <h3>Results</h3> Median overall survival (OS) improved from 6.7 mo (95% CI 4.6-8.7) in 1998- 2007 to 11.8 mo (95% CI 10.0-13.6) in 2008- 2018 (p<0.01). Mean DFl was 11.7 mo (SD 22.2 mo). Patients who recurred within 6 mo of receiving platinum chemotherapy had worse OS compared to those sensitive to platinum agents (6.9 vs 11.1 mo, p<0.05). Predictors of worse OS included HPV negativity (HR 1.5, 95% CI 1.1-2.2), high NLR (HR 1.0, 95% CI 1.0-1.1), DFI ≤6 mo (HR 1.4, 95% CI 1.0-1.9), and poor performance status (ECOG ≥2, HR 1.8, 95% CI 1.0-3.0). Patients with oligometastatic disease amenable to local treatment had improved OS over those receiving systemic therapy (26.1 vs 12.1 mo, p<0.01). Immune checkpoint inhibitor (ICI) in combination with EGFR inhibition was associated with the longest time on treatment compared to other systemic therapies (265 vs 120 d, p<0.001). HPV+ patients were more likely to respond to ICI compared to HPV- (243 vs 119 d, p<0.05). Patients with locoregional recurrence and/or bone metastases were more likely to respond to ICIs compared to other systemic therapies (p=0.01). Platinum sensitive patients were more likely to respond to VEGF inhibition compared to platinum refractory (196 vs 76 d, p<0.05). <h3>Conclusion</h3> These data support the promising activity of novel agents in R/M HNC while highlighting the efficacy of ICIs and improved survival of patients over time. The patterns of distant metastasis and treatment failures in R/M HNC can help guide development of surveillance guidelines especially with the advent of non-invasive biomarkers.