Aggressive thyroid carcinoma, which includes multiple subtypes, is associated with significant morbidity and mortality, and research is ongoing in the search for an effective treatment. Distinct immune profiles have been identified in certain subtypes of thyroid carcinoma, suggesting they may be susceptible to immune checkpoint inhibition. Unfortunately, a recent phase II study suggested a narrower focus may be needed.
Dr Kartik Sehgal and colleagues conducted a single-center, nonrandomized clinical trial to evaluate the efficacy and safety of dual immune checkpoint inhibition in 51 patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC), with exploratory cohorts in patients with medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC). The study did not meet its primary endpoint in patients with RAIR DTC, but the researchers noted that the results observed in patients with ATC may merit further evaluation. Patients with advanced ATC receiving dual immune checkpoint inhibition therapy had an overall response rate of 30%, and clinical benefit was realized in 50% of patients. This may potentially be attributed to the higher degree of tumor-infiltrating immune cells in ATC, but confirmatory research is needed.
High level
Although the primary endpoint was not met, the results of this study are valuable in helping to provide guidance for future research of immune checkpoint inhibitors in the treatment of aggressive thyroid carcinoma. More specifically, on the basis of these study results, the treatment of ATC with dual immune checkpoint therapy should be explored further in a larger clinical trial. Conversely, the authors concluded that further investigation of this therapeutic approach in nonbiomarker-selected DTC and MTC populations will not be worthwhile.
Ground level
While further investigation is needed, the study authors expressed optimism that dual immune checkpoint inhibition may emerge as a new treatment paradigm for patients with ATC, especially those whose tumors do not harbor targetable alterations and/or are not candidates for multikinase inhibitors. However, on the basis of these phase II study results, this therapeutic approach to treatment of other aggressive thyroid carcinoma subtypes is not currently recommended.
