Immunotherapy in Initial Treatment of Anaplastic Thyroid Cancer: Evaluation of Overall Survival in a National Cancer Database Study

Background: Anaplastic thyroid cancer (ATC) is an aggressive malignancy with a median survival of six months. While immunotherapy (IT) has improved outcomes in other solid tumors, its role in ATC remains unclear. This study evaluated whether receipt of IT was associated with improved overall survival (OS) in the initial treatment of patients with newly diagnosed ATC. Methods: We performed a retrospective study of patients with metastatic and nonmetastatic ATC from the National Cancer Database (2008-2020) treated with surgery, radiation, chemotherapy, or a combination. Patient outcomes were stratified between those who received IT at any point in their treatment compared with those who did not. The primary outcome was OS, compared between cohorts receiving IT and those who did not. Survival analyses were performed using Kaplan-Meier estimates, long-rank tests, and multivariable models. Results: Among 3318 patients with ATC, 87 (2.6%) received IT. Rates of surgical resection (46%) and radiation therapy (64% vs. 57%, p = 0.133) were similar across groups. IT recipients were younger (mean = 66.7 vs. 70.2 years, p = 0.005), more often diagnosed in recent years (2017-2019 vs. 2008-2016, p = 0.0001), and more frequently received chemotherapy (65.5% vs. 46.3%, p = 0.0007). Charlson Comorbidity Index scores were similar (p = 0.551). Median OS was 9.1 months (confidence interval [CI] 7.06-14.9) for those receiving IT versus 3.78 months (CI: 3.52-4.01) for those who did not (p < 0.005). Five-year OS was 18% (CI: 5-36%) with IT versus 9% (CI: 8-10%) without (p < 0.0001). Among 23 patients who received trimodality therapy (surgery, IT, and radiation), 5-year OS was 35% (CI: 16-55%) versus 9% in patients who did not. Conclusions: IT was associated with prolonged survival in patients with ATC, although confounding factors, such as the retrospective design of the study, lack of detailed IT drug details, and sequencing of therapy, preclude definitive conclusions on its efficacy. The efficacy of IT for ATC as a stand-alone treatment is uncertain. Further studies could indicate which combination of therapies best increases OS in patients with ATC.