Abstract 166P
Background
In the phase 3 EMERALD-1 study (NCT03778957), D + B + TACE significantly improved progression-free survival (PFS) vs TACE. In uHCC, liver function is often impaired; TACE may further deteriorate liver function and the underlying liver disease. Here, we evaluated the efficacy and safety of D + B + TACE by liver function in uHCC.
Methods
Pts with embolisation-eligible uHCC were randomised 1:1:1 to the D + B + TACE, D + TACE or PBOs + TACE (TACE) arms. Pts received D (1500 mg) or PBO for D (Q4W) + TACE. After completion of last TACE, pts received D (1120 mg) + PBO for B, D (1120 mg) + B (15 mg/kg), or PBOs for D and B (Q3W). PFS and time to progression (TTP) in pts in the D + B + TACE and TACE arms of the intent-to-treat (ITT) population, and safety in pts who received D + B + TACE or TACE in the safety analysis set (SAS; pts who received ≥1 dose of study treatment [tx], by tx received, regardless of randomisation) are reported by albumin-bilirubin (ALBI) grade (gr) 1 or 2 at baseline (no pts had ALBI gr 3 in the D + B + TACE or TACE arms).
Results
Baseline characteristics were generally consistent across tx arms, regardless of ALBI gr. PFS and TTP improved with D + B + TACE vs TACE in the ALBI gr 1 and 2 groups (Table). The rates of tx-emergent hepatic events were numerically higher in pts treated with D + B + TACE vs TACE in the ALBI gr 1 (37.8% vs 19.5%) and 2 (48.4% vs 28.6%) groups, consistent with the longer median duration of exposure (mDoE) to D with D + B + TACE vs TACE (Table); however, these events were predominantly low-grade. Rates of tx-related gr 3 or 4 hepatic events were comparable across tx arms regardless of baseline ALBI gr; no tx-related gr 5 hepatic events occurred in pts treated with D + B + TACE. Table: 166P
| ALBI gr 1 | ALBI gr 2 | |||
| ITT | D + B + TACE (n=117) | TACE (n=126) | D + B + TACE (n=87) | TACE (n=79) |
| Median PFS ∗ , mo (95% CI) | 17.4 (12.5–22.1) | 9.2 (6.9–13.6) | 11.1 (7.2–15.7) | 7.2 (6.7–11.1) |
| PFS HR vs TACE (95% CI) | 0.76 (0.56–1.05) | 0.76 (0.52–1.09) | ||
| Median TTP ∗ , mo (95% CI) | 22.1 (16.6–27.6) | 9.5 (7.0–14.1) | 19.4 (13.9–25.1) | 10.0 (6.9–16.3) |
| TTP HR vs TACE (95% CI) | 0.65 (0.47–0.92) | 0.57 (0.36–0.88) | ||
| SAS | D + B + TACE (n=90) | TACE (n=123) | D + B + TACE (n=64) | TACE (n=77) |
| mDoE to D or PBO for D, mo | 17.28 | 9.79 | 10.89 | 7.75 |
| mDoE to B or PBO for B, mo | 11.84 | 8.87 | 6.62 | 7.59 |
∗Assessed by blinded independent central review per RECIST v1.1.CI, confidence interval; HR, hazard ratio; RECIST, Response Evaluation Criteria in Solid Tumors.
Conclusions
These results support a favourable risk-benefit profile with D + B + TACE in embolisation-eligible uHCC regardless of baseline ALBI gr.
Clinical trial identification
NCT03778957.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Derrick Bond, PharmD, CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eisai, Roche, Ipsen; Financial Interests, Personal, Research Grant: Eisai, MSD. T. Decaens: Financial Interests, Personal, Advisory Board: BMS, Bayer, Becton Dickinson, AstraZeneca, Ipsen, Roche, Sirtex, Terumo, Guerbet; Financial Interests, Personal, Expert Testimony: Ipsen; Financial Interests, Personal, Invited Speaker: AbbVie, Gilead, MSD; Financial Interests, Institutional, Research Grant: ArQule, Guerbet, Genoscience Pharma. 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. J.P. Erinjeri: Financial Interests, Personal, Advisory Board: AstraZeneca. R. Lencioni: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Consulting or advisory role: AstraZeneca. 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, Principal Investigator: MSD, BMS, SIRTEX Medical, AstraZeneca. V.V. Breder: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Bayer, Eisai, Roche; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Bayer, Eisai, Roche; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, Bayer, Eisai, Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca. J. Heo: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Other, Consultan: GSK. V. Mazzaferro: Financial Interests, Personal and Institutional, Other, Advisory board (March 2023): Roche Ltd. J. Park: Financial Interests, Institutional, Principal Investigator: Ono-BMS, AstraZeneca, Eisai, Roche, Eisai, MSD; Financial Interests, Personal, Advisory Board: Roche, BeiGene, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Bayer. Y. Inaba: Financial Interests, Institutional, Invited Speaker: Eisai, AstraZeneca, Chugai. F. Dayyani: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca; Financial Interests, Personal, Invited Speaker: Ipsen, Sirtex, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, Bayer, Exelixis, Roche, Ipsen, Signatera, Merck, Taiho. M. Żotkiewicz: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. C.L. McCoy: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Makowsky: Financial Interests, Personal, Other, Former employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex, Terumo, Bayer, Adaptimmune; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, Incyte, AstraZeneca, Astellas Pharma, AstraZeneca, BMS, Boston Scientific, Roche; Financial Interests, Institutional, Research Grant: BMS, Sirtex. All other authors have declared no conflicts of interest.