A Role for Immune-Oncology + Locoregional Therapy in HCC - Episode 3

The TARE IO and TACE IO Combination Therapies


Riccardo Lencioni, MD: All locoregional interventions from local ablation with radiofrequency, or microwaves, or cryotherapy to regional treatments with [transarterial] chemoembolization [TACE] or [transarterial] radioembolization [TARE], have been shown in experimental settings and also in very early phase clinical settings, to be able to potentially have a synergistic effect with checkpoint inhibitors. The mechanisms involved include increasing antigen presentation, increasing the T-cell activation. The hypothesis is that combining locoregional therapy with checkpoint inhibitors will have not only an additive effect but a true synergistic effect. And this is why several investigator-initiated studies, mostly phase I or phase II studies, have been started combining different regimens, different interventional procedures, mostly chemoembolization or radioembolization and a variety of different regimens, including checkpoint inhibitors.

These studies are extremely important to, first of all, provide evidence that there is a true synergistic effect in the combination of locoregional and systemic therapy with checkpoint inhibitors. At the same time, they will hopefully elucidate which patient population is having the maximum benefit from which therapy. At this point, chemoembolization is accepted as a standard care for patients with intermediate stage HCC [hepatocellular carcinoma], meaning those patients who are unsuitable for radical therapy with surgery or ablation but still have disease limited to the liver with no extrahepatic spread, and at the same time the liver function is preserved. These are the patients for whom the combination of TACE with checkpoint inhibitors is expected to boost their survival expectations in terms of progression-free survival and overall survival.

For radioembolization with Y-90 [yttrium-90], trials in the advanced stage settings comparing Y-90 with sorafenib were negative. So, for this radioembolization procedure, the ability to be associated with a synergistic effect with checkpoint inhibitors is key to better understand which patients can truly benefit from this approach. Clearly, the local effect of radioembolization with Y-90 is highly significant. However, the patient population with cirrhosis and HCC is exposed to recurrences, and without a systemically active regimen in place that is able to sustain the response, unfortunately, survival outcomes are unsatisfactory at this point.

I don’t believe that we have information that is able to suggest which patient groups or subgroups will have the best benefit from a given approach. Meaning that the ongoing studies are critical, 1) to demonstrate there is truly a synergistic effect between locoregional therapies, particularly chemoembolization or radioembolization, and checkpoint inhibitors but also, 2) to clarify what is the best patient population for either approach.

Transcript Edited for Clarity