Combining Radioembolization and Immune Checkpoint Inhibitors for the Treatment of Hepatocellular Carcinoma: The Quest for Synergy

Hepatocellular carcinoma (HCC) is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of Y-90 radioembolization (Y-90-RE) and systemic therapy in the form of immune checkpoint inhibitors (ICI) have expanded treatment options for patients with an otherwise poor prognosis. Despite these gains, ICIs and Y-90-RE each have key limitations with low objective response rates and persistent hazard of out-of-field recurrence, respectively, and overall survival remains low. However, each therapy's strength can mitigate the other's weakness, making them ideal partners for combination treatment strategies. This review discusses the scientific and clinical rationale for combining Y-90-RE with ICIs, highlights early clinical trial data on its safety and efficacy, and proposes key issues to be addressed in this emerging field. With optimal strategies, combination therapies can potentially result in durable and curative outcomes in later stage patients rarely achieved just a decade ago.