Abstract 199P
Background
In EMERALD-1 (NCT03778957), D + B + TACE significantly improved progression-free survival (PFS) vs TACE in pts with embolisation-eligible uHCC. The up-to-7 criterion measures tumour burden based on tumour number and diameter, which are prognostic for HCC.
Methods
Pts were randomised 1:1:1 to D + B + TACE, D + TACE or TACE arms. Pts received D (1500 mg) + TACE or placebo (PBO) for D (Q4W) + TACE. After completing last TACE, pts received D (1120 mg) + B (15 mg/kg), D (1120 mg) + PBO for B or PBOs for D and B (Q3W). PFS and time to progression (TTP) by BICR RECIST v1.1 in the D + B + TACE and TACE arms of the intent-to-treat (ITT) cohort, and safety in pts who received D + B + TACE or TACE in the safety analysis set (pts received ≥1 dose of study treatment [tx], regardless of randomisation) are reported by baseline tumour burden within (≤7) or beyond up-to-7 criterion (>7). Efficacy in the >7 group is also reported by <10 cm and ≥10 cm max tumour diameter.
Results
At screening, the >7 group included more pts with ECOG PS 1, BCLC Stage C, HAP C or D scores or PVI vs the ≤7 group. Disease characteristics were generally consistent between arms within each tumour burden group. PFS and TTP improved with D + B + TACE vs TACE in the ≤7 and >7 groups. In the >7 group, consistent PFS and TTP benefit was seen in D + B + TACE vs TACE in pts with max tumour diameter <10 cm and ≥10 cm. Max Grade 3–4 tx-related adverse event frequencies were higher with D + B + TACE vs TACE in the ≤7 (24.4% vs 9.1%) and >7 groups (29.2% vs 3.0%); differences were reduced when adjusted for exposure (event rate per 100 pt year, ≤7 group: 15.9 vs 6.5; >7 group: 21.6 vs 3.4). No tx-related deaths with D + B + TACE were observed Table: 199P
| ITT | ≤7 | >7 | >7 with <10 cm max tumour diameter | >7 with ≥10 cm max tumour diameter | ||||
| D + B + TACE n=97 | TACE n=102 | D + B + TACE n=106 | TACE n=103 | D + B + TACE n=65 | TACE n=68 | D + B + TACE n=41 | TACE n=35 | |
| mPFS (95% CI), month | 19.4 (13.9–24.9) | 11.1 (7.0–14.0) | 11.1 (6.7–16.6) | 6.9 (5.2–8.5) | 11.1 (6.7–18.9) | 8.5 (6.9–16.3) | 11.1 (4.4–16.6) | 4.8 (2.9–6.9) |
| PFS HR (95% CI) | 0.72 (0.51–1.03) | 0.79 (0.57–1.09) | 0.88 (0.58–1.33) | 0.66 (0.38–1.15) | ||||
| mTTP (95% CI), month | 24.9 (19.4–30.2) | 11.1 (7.1–16.6) | 16.7 (12.5–22.3) | 8.2 (6.9–14.1) | 16.7 (11.0–22.4) | 15.4 (7.2–16.7) | 16.6 (11.1–not calculable) | 5.1 (3.0–7.1) |
| TTP HR (95% CI) | 0.59 (0.40–0.87) | 0.64 (0.44–0.93) | 0.75 (0.46–1.20) | 0.46 (0.23–0.90) | ||||
CI, confidence interval; HR, hazard ratio; m, median
.Conclusions
PFS and TTP benefit was observed with D + B + TACE vs TACE with manageable safety, regardless of tumour burden and max tumour diameter. Data further support a favourable risk-benefit profile with D + B + TACE in embolisation-eligible uHCC.
Clinical trial identification
NCT03778957.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Justine Juana, BHSc, CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. R. Lencioni, J. Erinjeri: Financial Interests, Personal, Advisory Board: AstraZeneca. S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD, Roche; Financial Interests, Personal, Invited Speaker: Astra-Zeneca, MSD, Eisai, Roche, Ipsen; Financial Interests, Personal, Research Grant: Eisai, MSD. Z. Ren: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, MSD. Roche. J. Heo: Financial Interests, Personal, Research Grant: Roche, Gilead; Financial Interests, Personal, Other, Consulting fees: AbbVie Korea; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Gilead, Roche, and Yuhan Korea; Financial Interests, Personal, Other, Leadership or fiduciary role in other board, society, committee or advocacy group: AstraZeneca. V.V. Breder: Financial Interests, Personal, Advisory Board, payment for lectures: Roche, AstraZeneca, Eisai, Bayer, Novartis. M. Bouattour: Financial Interests, Personal, Advisory Board: MSD, BMS, Sirtex Medical, Ipsen, AbbVie, AstraZeneca, Servier, Taiho; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Principal Investigator: MSD, BMS, Sirtex Medical, AstraZeneca. F. Dayyani: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca; Financial Interests, Personal, Invited Speaker: Ipsen, Sirtex, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Bayer, Roche, Ipsen, Merck; Financial Interests, Institutional, Coordinating PI: Exelixis, Signatera, Taiho. T. Suttichaimongkol: Financial Interests, Personal, Other, Honoraria: Takeda (Thailand). T. Decaens: Financial Interests, Personal, Advisory Board: BMS, Bayer, Becton Dickinson, AstraZeneca, Ipsen, Roche, Sirtex, Terumo, Guerbet; Financial Interests, Personal, Invited Speaker: AbbVie, Gilead, MSD; Financial Interests, Institutional, Research Grant: ArQule, Guerbet, Genoscience Pharma. R. Griffin: Financial Interests, Personal, Other, Contracted employee: AstraZeneca. C. Morgan, S.K. Ali, K. Balaji: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche. All other authors have declared no conflicts of interest.