Outcomes by baseline alpha-fetoprotein (AFP) levels in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (HCC)

Abstract

Background: High baseline AFP levels are associated with poor prognosis in patients with HCC and are associated with a distinct molecular profile. C, an inhibitor of MET, VEGF receptors, and AXL, improved overall survival (OS) and progression-free survival (PFS) compared with P in the phase 3 CELESTIAL trial (NCT01908426). Median OS was 10.2 mo with C vs 8.0 mo with P (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.63-0.92; p=0.0049), and median PFS was 5.2 mo with C vs 1.9 mo with P (HR 0.44, 95% CI 0.36-0.52; p<0.0001) (Abou-Alfa, JCO 2018, ASCO GI abstract 207). Method(s): 707 patients were randomized 2:1 to receive C (60 mg qd) or P. Eligible patients had pathologic diagnosis of HCC, Child-Pugh score A, and ECOG performance status =20 ng/mL, 49% had AFP >=200 ng/mL, and 41% had AFP >=400 ng/mL. For patients with baseline AFP <400 ng/mL, median OS was 13.9 mo with C vs 10.3 mo with P (HR 0.81), and median PFS was 5.5 mo with C vs 1.9 mo with P (HR 0.47). For patients with baseline AFP >=400 ng/mL, median OS was 8.5 mo with C vs 5.2 mo with P (HR 0.71), and median PFS was 3.9 mo with C vs 1.9 mo with P (HR 0.42). C also improved OS vs P in patients with AFP >=200 ng/mL or >=20 ng/ mL, and C improved PFS irrespective of AFP levels (Table). Patients with high baseline AFP experienced high-grade transaminitis more frequently in both treatment groups; grade 3/4 elevated aspartate aminotransferase with C vs P was 8% vs 4% for AFP <400 ng/mL and 17% vs 11% for AFP >=400 ng/ mL. Conclusion(s): C improved OS and PFS vs P in patients with previously treated advanced HCC across a range of baseline AFP levels. High AFP levels were associated with a larger treatment benefit with C for both OS and PFS. (Table Presented).