Goals for TACE and Immunotherapy Trial in Intermediate-Stage HCC

Arndt Vogel, MD, managing senior consultant and professor in the Department of Gastroenterology, Hepatology, and Endocrinology at Hannover Medical School, discusses the IMMUTACE (NCT03572582) study investigating the efficacy of transarterial chemoembolization (TACE) with nivolumab (Opdivo) in patients with intermediate-stage hepatocellular carcinoma (HCC).

IMMUTACE is a phase 2 single-arm, open label study of TACE in combination with nivolumab. TACE is the most common first-line treatment for HCC, and nivolumab is an anti–PD-1 agent. The trial was designed to evaluate if the combination improved the effect of TACE on tumors. According to Vogel, TACE could target and damage tumors while priming the immune system to receive nivolumab more effectively.

In the study, 49 patients were administered TACE, and after 2 to 3 days, 240 mg of nivolumab was administered intravenously every 2 weeks. TACE was repeated after 8 weeks. The primary end point was overall response rate (ORR). The investigators were looking at whether the combination showed efficacy of over 55% ORR. Vogel explains that the patients were able to achieve an ORR of over 70%, reaching the primary end point.

These results are preliminary, and other secondary end points such as overall survival, have not yet been reached. The study will continue for a maximum of 42 months. While this is a single-arm study, other ongoing studies will compare TACE alone with various combinations, and more data will be collected in future phase 3 studies.

TRANSCRIPTION:

0:08 | We tried to combine basically the best of both treatment approaches, specifically in patients with liver-limited disease. The idea was to use TACE to get control of the tumor. Maybe also destroy the tumor a little bit, which should lead to an antigen release [and] could prime the immune system to the checkpoint inhibitor, which we applied after the first TACE. Patients were allowed to receive that second TACE when it was considered reasonable by the investigator and then nivolumab was continued. And the idea was really to combine immunotherapy with local therapies to get a better disease control.

Since this was a proof-of-concept study, we used ORR as a primary end point, and we assumed a response rate of more than 55% as clinically meaningful. In the end, we were able to achieve a response rate of over 70%, indicating that the study met it primary end point. Based on the data we have seen so far, I think it looks like a very promising combination which should be pursued in subsequent and also phase 3 studies.