Y90 and Immune Checkpoint Inhibitor Synergy Is the Future

Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma

Clinical question

Is combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (90Y) radioembolization superior in outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and 90Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC).

Take away point

 Patients with HCC who received 90Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received 90Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.

Reference

Garcia-Reyes, K., Gottlieb, R. A., Menon, K. M., Bishay, V., Patel, R., Patel, R., Nowakowski, S., Sung, M. W., Marron, T. U., Gansa, W. H., Zhang, J., Raja, S. C., Shilo, D., Fischman, A., Lookstein, R., & Kim, E. (2024). Radioembolization plus immune checkpoint inhibitor therapy compared with radioembolization plus tyrosine kinase inhibitor therapy for the treatment of hepatocellular carcinoma. Journal of Vascular and Interventional Radiology.

Click here for abstract: Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma - Journal of Vascular and Interventional Radiology (jvir.org)

Study design

A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent 90Y 4 weeks within initiation of ICI or TKI therapy were included.

Funding Source

None listed

Setting

Academic, The Mount Sinai Hospital

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Summary/Commentary

In Garcia-Reyes et al. 2024’s Journal of Vascular and Interventional Radiology (JVIR) article, they provided limited retrospective evidence on the superiority of Yttrium-90 radioembolization in combination with immune checkpoint inhibitors over the combination of Yttrium-90 with Tyrosine Kinase inhibitors. In the figure above, it showed the superiority in both overall survival and progression-free survival curves for Yttrium-90 with the immune checkpoint inhibitors over the tyrosine kinase inhibitors when compared in the early time frame. This initial effect did not persist long enough to statistically affect disease progression or survival outcomes but the trend remained in favor of Yttrium-90 radioembolization and immune checkpoint inhibitors combination therapy. The main statistically significant finding was improved imaging responses. Yttrium-90 plus immune checkpoint inhibitor combination therapy also caused significantly fewer regimen-modifying adverse effects than Yttrium-90 plus tyrosine kinase inhibitor treatment and significantly fewer overall adverse events. 63.2% of patients in the yttrium-90 plus tyrosine kinase inhibitor group terminated systemic therapy owing to adverse effects, which was significantly higher than the 5.3% in the yttrium-90 plus immune checkpoint inhibitor group. Such improved treatment adherence and quality of life of patients undergoing combination therapy for advanced hepatocellular carcinoma will be the focus of ongoing and future clinical trials, in addition to progression free and overall survival.

The pathophysiology behind the combination therapy is intriguing, that the “locoregional therapies including ablation, transarterial chemoembolization, and yttrium-90 radioembolization may help prime the immune system and improve the effectiveness of immune checkpoint inhibitor therapies in the treatment of unresectable Hepatocellular Carcinoma.” This theory was supported by Craciun et al. who found an increase in granzyme B+ lymphocytes in the tumor as well as higher numbers of CD4 and CD8+ T cells in resected tissue after radioembolization compared to those found in patients who underwent chemoembolization or no pre-resection treatment. As there are additional studies on yttrium-90 in combination with other immune checkpoint inhibitors (i.e. yttrium-90 before durvalumab plus tremelimumab (ROWAN, NCT05063565)), the synergistic effects between radioembolization and immune checkpoint inhibitors will be further delineated. The idea that the destruction of the cancer cell induced by the radioembolization results in recruitment of immune cells to the tumor microenvironment as well as enhancing tumor immunogenicity (through increasing tumor antigen release) is profound. The promising results so far may prompt new guidelines in favor of the combination of yttrium-90 and immune checkpoint inhibitors. Furthermore, advances in the context of advanced hepatocellular carcinoma open the possibility of applying the concept of radioembolization with immune checkpoint inhibitors to other malignancies as well.

Post Author

Tony Nguyen

PGY-1

Integrated Interventional Radiology Resident

UMass Chan Medical School