Trends in end-of-life immunotherapy use in metastatic head and neck squamous cell carcinoma: A National Cancer Database analysis.

Abstract

6035 Background: Aggressive systemic cancer treatment near the end of life (EOL) rarely benefits patients and is an established marker of low-quality healthcare. While EOL chemotherapy use has substantially declined over time, EOL immunotherapy administration has increased in the era of immune checkpoint inhibitors (ICIs). For metastatic head and neck squamous cell carcinoma (mHNSCC), a high-burden disease with rapidly expanding approvals, ICIs have emerged as a compelling mainstay of treatment. However, these expansions may have increased nonbeneficial ICI use among end-stage patients, contributing to quality impacts like decreased hospice enrollment and high financial burden. Given recent evolutions in head and neck cancer care, we conducted a retrospective cohort study to examine temporal trends and factors associated with EOL immunotherapy initiation in mHNSCC. Methods: Patients diagnosed with mHNSCC who received first-course immunotherapy between 2016-2022 were identified in the National Cancer Database. EOL-initiated immunotherapy was defined as initiation within 1 month of death. Two-sample t- or χ² testing was used for comparison of means and proportions, respectively, between EOL and non-EOL immunotherapy initiation groups. Multivariable logistic regression with a priori covariate selection was used to identify factors associated with EOL immunotherapy initiation. Sensitivity analyses were conducted with 2 and 3-month EOL thresholds. Results: Among 8806 included patients, 29.3% received immunotherapy, rising from 17.7% in 2016 to 40.9% in 2022 following first-line FDA ICI approvals. By 2021, EOL-initiated immunotherapy occurred among 6.7%, 13.0%, and 16.4% of treated patients at 1-, 2-, and 3-month EOL thresholds, with possible upward trends after 2019 (2021 vs 2019, 1-month EOL, p=0.114; 2-month EOL, p<0.05, χ² test). In regression analysis, predictors of one-month EOL initiation included female sex (odds ratio [OR]=2.09, 95% CI=1.33–3.27), disadvantaged insurance status (Medicaid/other governmental OR=2.27, 95% CI=1.18–4.35; uninsured/unknown OR=5.09, 95% CI=2.33–11.12), high metastatic burden (≥3 sites OR=8.77, 95% CI=2.94–26.12), and surgical treatment (OR=2.12, 95% CI=1.19–3.79). Protective factors included academic setting (OR=0.60, 95% CI=0.40–0.90), oropharyngeal primary site (OR=0.54, 95% CI=0.32–0.92), and concurrent radiotherapy (OR=0.53, 95% CI=0.35–0.79) or chemotherapy (OR=0.48, 95% CI=0.31–0.73). Conclusions: EOL-initiated immunotherapy occurs among a small but notable proportion of mHNSCC patients and is associated with various indicators of clinical and demographic vulnerability. As ICI use expands, our findings underscore the importance of optimizing patient selection, EOL treatment guidelines, and system-level practices to ensure judicious use of immunotherapy in terminal settings.