Evaluating the Efficacy of Immunotherapy in Head and Neck Cancer Stratified by Smoking Status

Introduction: Smoking is a known risk factor for several adverse health outcomes, including head and neck cancer (HNC). This study aims to deepen our understanding of the impact of tobacco exposure on outcomes in HNC patients receiving immune checkpoint inhibitor (ICI) therapy.

Methods: The TriNetX Database was queried for adult HNC patients who received ICI (Durvalumab, Pembrolizumab, Nivolumab, and Ipilimumab) from 2011-2023. Cohorts were separated by patients with and without a smoking history. Propensity score matching (PSM) was performed to account for factors such as TNM staging. Within the smoking cohort, patients were sub-stratified by if they continued or quit smoking following ICI treatment. Hazard ratios (HRs) and overall survival (OS) were analyzed through Kaplan-Meier analysis. Odds ratios (ORs) and 95% CIs were calculated for post treatment outcomes; p < 0.05 was considered significant.

Results: 2,244 smokers and 5,914 non-smokers met the inclusion criteria. After PSM, smokers with HNC had worse OS than non-smokers at 1, 3, and 5 years [(HR: 1.24 (1.14-1.34), (HR: 1.28 (1.20-1.37), (HR: 1.29 (1.21-1.38), respectively]. There was no difference in the rates of immune related adverse effects (IRAEs), development of secondary cancer, chemotherapy, radiation, and salvage excision surgery between smokers and non-smokers. Patients who continued smoking after ICI had increased risk IRAEs at 1, 3, and 5 years [(OR: 1.18 (1.02-1.36), (OR: 1.22 (1.05-1.41), (OR: 1.22 (1.05-1.41)] and salvage excision surgery at 1, 3, and 5 years [OR: 1.58 (1.04-2.39), (OR: 1.55 (1.07-2.25), (OR: 1.70 (1.17-2.46)]. There was no difference in OS, radiation and secondary cancer between patients who continued vs quit smoking following ICI.

Conclusions: Smokers with HNC who received ICI had worse OS compared to non-smokers. However, OS was similar between patients who continued smoking and quit smoking following ICI. Despite this, those who continued smoking following ICI experienced greater risk for IRAEs and salvage excision. Further studies are needed to characterize the influence of smoking status on ICI therapy.