Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
Masatoshi Kudo , Stephen Lam Chan , Bruno Sangro , Joseph P. Erinjeri , Shukui Qin , Zhenggang Ren , Yasuaki Arai , Valeriy Vladimirovich Breder , Shi-Ming Lin , Jean-Marie Peron , Tien Quang Nguyen , Lunan Yan , Chang-Fang Chiu , Florinda A. Santos , Anil Veluvolu , Satheesh Chiradoni Thungappa , Claire Morgan , Kerry Parsons , Ioannis Xynos , Riccardo Lencioni
Background: The global Phase 3 EMERALD-1 study (NCT03778957) primary endpoint was met: durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) significantly improved progression-free survival vs placebos (pbos) + TACE (median 15.0 vs 8.2 mo; HR, 0.77; 95% CI, 0.61–0.98; p=0.032 [threshold 0.0435]) in participants (pts) with embolization-eligible unresectable hepatocellular carcinoma (uHCC) with a manageable safety profile. This post hoc, exploratory analysis assessed safety in the study’s two treatment (tx) periods (pds): D-TACE (D-T) and D-B. Methods: Pts were randomized 1:1:1 to D+TACE, D+B+TACE, or pbos+TACE. In the D-T pd, pts received 1–4 TACE (cTACE or DEB-TACE [investigator choice]) plus D (1500 mg Q4W) or pbo for D. In the D-B pd, post-last TACE, pts received D (1120 mg Q3W) plus pbo for B, D (1120 mg Q3W) plus B (15 mg/kg Q3W), or pbos for D and B. Adverse events (AEs), start/end date, maximum/change in CTCAE grade, and causality were assessed in the D-T and D-B pds in pts who received any study tx in the arm to which they were randomized, until end of follow-up. Results: The Table shows duration of exposure (DoE). In the D+TACE, D+B+TACE, and pbos+TACE arms, AEs were reported by 144 (74.6%), 139 (72.0%), and 148 (74.0%) pts in the D-T pd and 133 (68.9%), 147 (76.2%), and 132 (66.0%) pts in the D-B pd; were possibly related (pos rel) to study tx in 59 (30.6%), 56 (29.0%), and 41 (20.5%) pts in the D-T pd and 76 (39.4%), 114 (59.1%), and 69 (34.5%) pts in the D-B pd; and were provoked by TACE in 72 (37.3%), 90 (46.6%), and 85 (42.5%) pts in the D-T pd and 16 (8.3%), 18 (9.3%), and 21 (10.5%) pts in the D-B pd, respectively. Conclusions: D+B+TACE had a manageable safety profile across the D-T and D-B pds, consistent with the individual agents and underlying disease. These data further support D+B+TACE as a new potential standard of care in embolization-eligible uHCC. Clinical trial information: NCT03778957.
D+TACE D-T pd (n=193) | D+B+TACE D-T pd (n=193) | Pbos+TACE D-T pd (n=200) | D+TACE D-B pd (n=193) | D+B+TACE D-B pd (n=193) | Pbos+TACE D-B pd (n=200) | |
---|---|---|---|---|---|---|
Median (range) DoE to D or pbo; to B or pbo, months | 2.76 (0.2–30.8) | 2.76 (0.2–25.3) | 2.76 (0.9–26.1) | 6.93 (0.7–45.5); 6.92 (0.7–45.5) | 10.51 (0.3–38.1); 9.35 (0.3–36.5) | 8.31 (0.7–43.0); 8.31 (0.7–43.0) |
Any AE, n (%) | ||||||
Max Grade 3/4 | 29 (15.0) | 29 (15.0) | 26 (13.0) | 36 (18.7) | 60 (31.1) | 22 (11.0) |
Pos rel to study tx, max Grade 3/4* | 4 (2.1) | 6 (3.1) | 4 (2.0) | 10 (5.2) | 38 (19.7) | 8 (4.0) |
With outcome of death | 9 (4.7) | 6 (3.1) | 5 (2.5) | 6 (3.1) | 16 (8.3) | 6 (3.0) |
Pos rel to study tx* | 0 | 2 (1.0)† | 1 (0.5)† | 1 (0.5)‡ | 0 | 2 (1.0)‡ |
Provoked by TACE | 0 | 0 | 1 (0.5) | 0 | 0 | 0 |
Leading to discontinuation of study tx | 11 (5.7) | 7 (3.6) | 5 (2.5) | 13 (6.7) | 42 (21.8) | 10 (5.0) |
Pos rel to study tx* | 1 (0.5) | 3 (1.6) | 2 (1.0) | 5 (2.6) | 18 (9.3) | 4 (2.0) |
*Excluding TACE. †Pos rel to D or pbo for D. ‡Pos rel to B or pbo for B.
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Abstract Disclosures
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