OncologyTube: [00:00:00] Okay, we’re here at ASCO GI 2024 and we have Dr. Dr. Riccardo Lencioni, MD medical doctor, professor of radiology and director of cancer imaging program at the Pisa University School of Medicine in Italy. Dr. Lencioni, thank you so much for joining us. My pleasure. Today we’ll be discussing the Emerald 1, a phase 3 randomized placebo controlled study of tastes combined with Dorvalumab with or without Bevacizumab in patients with unresectable hepatocellular cancer.
carcinoma eligible for embolization, which is featured here at ASCO GI 2024. Dr. Lencioni, can you provide the overview for the Emerald One trial?
Riccardo Lencioni, MD: Yes, sure. So the Emerald-1 was, a global phase three, double blinded placebo controlled randomized trial. of, durvalumab [00:01:00] plus or minus Bevacizumab in combination with a or trans chemoembolization.
we are talking about, patients, at the, so-called Intermediate Stage, who are, unsuitable for, radical therapy including, surgery or ablation. However, the disease is still confined to the liver and, for this patient population, which is. a good 20 to 30 percent of the 900, 000 new cases diagnosed with ACC.
every year worldwide for this patient population. The standard of care is arterial embolization, typically with days. Although the progression free survival after days does not exceed the 7 to 8 months. So there is a larger. Unmet need that we wanted to address with the Emerald One study. There is a rationale, to [00:02:00] combine, chemoembolization, with, immune checkpoint inhibitors and the VEGF inhibitors, that, we wanted to explore, in this phase three trial.
OncologyTube: Alright, so what is the significance of the Emerald 1 study findings regarding progression free survival in patients with unresectable hepatocellular carcinoma treated with combination of Dorvalumab, Bevacizumab, and TACE compared to TACE
Riccardo Lencioni, MD: alone? Yeah, correct. So the trial actually had three arms. So, arm A was, taste in combination with Durvalumab monotherapy.
The arm B was, taste in combination with Durvalumab and Bevacizumab and arm C was taste and placebo. So everybody got the standard of care, which is. Case. the primary endpoint, [00:03:00] was, progression-free survival for the combination of durvalumab and bevacizumab versus the control arm. And the emerald one study met the primary endpoint, so the data, showed statistically significant and clinically meaningful.
improvement, in progression, free survival, median PFS was 8. 2 months in the control arm, which is one of the best report and the results for taste alone, but increased by 6. 8 months up to 15 months, with the combination of Durvalumab. So, this is, a major improvement, that was, supported, by the secondary endpoints.
TTP, for instance, was, twenty Two months, in the combination arm versus ten in the control arm. [00:04:00] response rate was also higher, in the combination arm. and, the data suggests that, there is a truly synergistic effect, between, chemoembolization and, the combination of, durvalumab and babagizumab.
OncologyTube: Can you elaborate on the safety profile of the D plus B plus TACE regimen, particularly in terms of the percentage of patients experiencing grade 3, 4 treatment related adverse events and how it compares to other treatment options for UHCC?
Riccardo Lencioni, MD: Sure. So the percentage of grade 3, 4 treatment related adverse events, was, I think 26 percent in the combination of TACE, Durvalumab, and Bebacizumab arm.
And this compares well with other reported, safety profiles, in the setting, of this patient [00:05:00] population with unrespectable ACC. with other immuno based combinations. these events were, not, unexpected. and, the most common, like, hypertension and proteinuria. are well known, adverse reactions to, Bebacizumab or in other instances to Durvalumab.
So there were no new or unexpected safety signals. an important point that I wanted to emphasize. It’s that we had no grade five events, so there were no treatment related deaths, in the combination of TACE, Durvalumab, and Bebacizumab arm. And this was, you know, I think, a very important piece of information, given, you know, these vulnerable and fragile patient population who have, you know, two [00:06:00] diseases, the cirrhosis and the tumor.
OncologyTube: So what potential implications do the results of the Emerald One study have for the standard of care and the treatment of embolization eligible UHCC and how might this ICI based regimen change clinical practice in the field of hepatocellular carcinoma?
Riccardo Lencioni, MD: Yeah, I think Emerald One has opened a new horizon, demonstrating, for the first time.
That, there could be a synergistic effect between, local regional liver directed therapies and, systemically active drugs, and particularly immuno based combinations. this is, the first positive trial. in this patient population, the first phase three, positive trial in this patient population since 20 years.
so, I think, the, the data is very compelling [00:07:00] and, it will have a major impact. number one, I think at this point of time. systemic therapy with immune based combinations have shown potential benefit across all stages of ACC from the early stage in the adjuvant setting, intermediate ACC and advanced.
a multidisciplinary discussion, including, you know, all the different specialists involved in the management of ACC, becomes even more important as the armamentarium is actually at this point of time much broader. In this patient population, you know, when you move from clinical trials to clinical practice.
It’s always important to understand that the unique characteristics of the individual patient because sometimes the patient that you see in the clinic are not the same recruited, you know, with sharp [00:08:00] inclusion exclusion criteria in a clinical trial. So it’s very important, particularly for this combination.
to stick to the criteria. So patients with, you know, a good general condition, preserved liver function, and, and, to perform an endoscopy to understand the potential risk of bleeding. So, this, I think, individualized assessment is extremely important because clearly the data suggests that for those who are, eligible for this, combinational regimen, there could be a major advantage, in delaying tumor progression and, and, you know, hopefully providing a, you know, a better, outcome for, for their disease.
OncologyTube: All right. This has been an interview with Dr. Riccardo Lencioni, Medical Doctor, Professor of Radiology and Director of Cancer Imaging Program at the Pisa University School of Medicine in Italy. Dr. Lencioni, thank you so much for joining us today. Thank you
Riccardo Lencioni, MD: very much. Thank you.[00:09:00]