Outcomes by baseline tumor burden using the 6-and-12 score in EMERALD-1: A phase 3 study of durvalumab (D) ± bevacizumab (B) with transarterial chemoembolization (TACE) in embolization-eligible unresectable hepatocellular carcinoma (uHCC).

Abstract

4083 Background: In EMERALD-1 (NCT03778957), D + B + TACE significantly improved progression-free survival (PFS) vs TACE in participants (pts) with embolization-eligible uHCC. Tumor burden is a prognostic factor in HCC. Prior analyses showed improvements in PFS with D + B + TACE vs TACE in pts who met or exceeded the up-to-7 criterion (a measure based on tumor number and size), and in those with max tumor diameters of < 10 cm or ≥10 cm. The 6-and-12 score measures tumor burden based on tumor number and size. We assessed outcomes in EMERALD-1 by baseline tumor burden using the 6-and-12 score. Methods: Pts were randomized 1:1:1 to D + B + TACE, D + TACE, or TACE. Pts received D (1500 mg) or PBO for D (Q4W) + TACE. After completing the last TACE, pts received D (1120 mg) + B (15 mg/kg), D (1120 mg) + PBO for B, or PBOs for D and B (Q3W). In pts who received D + B + TACE and TACE, PFS, time to progression (TTP), and objective response rates (ORR), per BICR RECIST v1.1 in the intent-to-treat (ITT) population, and safety and number of TACE cycles in the safety analysis set (SAS; pts received ≥1 dose of study treatment [tx], regardless of randomization) are reported by baseline tumor burden using 6-and-12 scores: ≤6, > 6–12, or > 12. Results: Overall, 40.0%, 43.9%, and 16.2% of pts belonged to the ≤6, > 6–12, and > 12 groups, respectively. The number of pts who received ≥2 TACE cycles increased across the groups (≤6: 63.8%; > 6–12: 81.7%; > 12: 89.8%). PFS and TTP improved with D + B + TACE vs TACE, regardless of baseline tumor burden, with the best relative improvement in hazard ratios (HRs) in the > 12 group (Table). ORRs were higher for D + B + TACE vs TACE in all groups. Max Grade 3–4 tx-related adverse event (TRAE) frequencies were numerically higher with D + B + TACE vs TACE across tumor burden groups; differences were reduced when adjusted for exposure. No tx-related deaths occurred with D + B + TACE. Conclusions: PFS, TTP, and ORR benefits were seen with D + B + TACE vs TACE with manageable safety, regardless of tumor burden, further supporting a favorable risk-benefit profile with D + B + TACE in embolization-eligible uHCC. Clinical trial information: NCT03778957 . ≤6 >6–12 >12 ITT D + B + TACE n=81 TACE n=82 D + B + TACE n=84 TACE n=95 D + B + TACE n=38 TACE n=28 Median PFS (95% CI), months 19.4(13.7–24.9) 11.1 (7.0–13.6) 13.9 (7.2–19.6) 9.7(6.9–16.3) 11.1 (4.4–16.6) 4.8 (2.9–6.9) PFS HR vs TACE (95% CI) 0.69(0.47–1.01) 0.85(0.59–1.22) 0.61 (0.33–1.13) Median TTP (95% CI), months 22.1(15.1–30.5) 11.1(7.0–13.9) 22.0(13.9–27.7) 15.4(7.2–16.7) 16.6(6.9–25.1) 5.1(3.0–7.1) TTP HR vs TACE (95% CI) 0.60(0.40–0.90) 0.66(0.43–1.01) 0.42(0.20–0.87) ORR, n (%)* 47 (58.8) 27 (33.8) 31 (36.9) 32 (33.7) 10 (26.3) 1 (3.6) SAS n=71 n=81 n=61 n=92 n=22 n=27 Max Grade 3–4 TRAE, n (%) event rate per 100 pt-years 17 (23.9)15.9 9 (11.1)7.9 17 (27.9)19.9 3 (3.3) 3.1 7 (31.8)22.2 0 *In pts with evaluable disease at baseline.