Patterns of radiological progression in participants (pts) with embolization-eligible hepatocellular carcinoma (HCC) treated with durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) and placebos + TACE: EMERALD-1 post hoc analysis.
Authors: Sangro Bruno , Bouattour Mohamed , Park Joong-Won , Diaz Dr. Consuelo , Erinjeri Joseph P. , Alves Gustavo Vasconcelos , Gu Shan-Zhi , Manikhas Aleksei , Kuroda Hidekatsu , Suksombooncharoen Thatthan , Vo Truc Hoi Trung , Ostwal Vikas S. , Eastgate Melissa A. , Vaccaro Gina M. , Griffin Rebecca , Ali Sajid , Balaji Kavitha , Chan Stephen Lam 
Published: January 2025

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Background:
EMERALD-1 (NCT03778957) met its primary endpoint, demonstrating improved progression-free survival (PFS) in pts with locoregional HCC treated with D + B + TACE versus placebos (PBO) + TACE (stratified Cox proportional hazards hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.98 [Lencioni R, et al.
J Clin Oncol
2024;42(suppl 3). Abs LBA432]). This post hoc analysis assessed outcomes by radiological progression pattern in pts treated with D + B + TACE or PBO + TACE.
Methods:
Pts included in this analysis received D (1500 mg) or PBO for D (Q4W) in combination with conventional (c)- or drug-eluting bead (DEB)-TACE (investigator choice, 1–4 TACE procedures within 16 weeks). Subsequently, pts received D (1120 mg) + B (15 mg/kg), or PBO for D + B (Q3W). This study analyzed radiological progression patterns at the time of first progressive disease (PD) as assessed by the investigator per modified Response Evaluation Criteria in Solid Tumors. A new lesion was classified as a new intrahepatic lesion (NIH) or new extrahepatic lesion (NEH); tumor growth of existing intrahepatic lesions (increase of ≥20% of an existing target lesion with at least >5 mm absolute increase or unequivocal PD with a non-target lesion) was classified as intrahepatic growth (IHG; categories were not mutually exclusive). Efficacy was assessed by time to progression (TTP).
Results:
In the D + B + TACE arm, 53.9% of pts had PD, and in the PBO + TACE arm 79.0% of pts had PD. The most common pattern of disease progression across both treatment arms was NIH, occurring in 73 (35.8%) and 107 (52.2%) pts in the D + B + TACE and PBO + TACE arms, respectively, with 31 (15.2%) and 34 (16.6%) pts exhibiting IHG, and 24 (11.8%) and 39 (19.0%) pts exhibiting NEH, respectively. Improved TTP was observed in pts treated with D + B + TACE versus PBO + TACE, regardless of progression pattern (Table).
Conclusions:
Overall, the rate of progression was lower with D + B + TACE compared with PBO + TACE. The pattern of disease progression observed with D + B + TACE and PBO + TACE was similar, with NIH the most common pattern of progression in both treatment arms. Consistent benefit in TTP was observed with D + B + TACE versus PBO + TACE, regardless of progression pattern.
Clinical trial information: NCT03778957
.

NIH

IHG

NEH

D + B + TACE (n=73)

PBO + TACE (n=107)

D + B + TACE (n=31)

PBO + TACE (n=34)

D + B + TACE (n=24)

PBO + TACE (n=39)

Median (95% CI) TTP, months
13.7 (10.8–16.5)
8.8 (7.0–10.9)
5.1 (3.0–9.0)
4.3 (2.9–4.8)
6.7 (2.8–16.6)
4.6 (2.9–6.8)

HR (95% CI)*
0.78 (0.57–1.07)

0.61 (0.36–1.03)

0.66 (0.36–1.15)

*HR and CI were estimated using a Cox proportional hazards model, the CI was calculated using a profile likelihood approach.