Outcomes based on Albumin‐Bilirubin (ALBI) grade in the phase 3 CELESTIAL trial of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (HCC)

Abstract

Introduction: ALBI grade is an objective measure of liver function developed for patients with HCC; higher ALBI grade is associated with worse prognosis (Johnson, 2015). In the phase 3 CELESTIAL trial (NCT01908426), cabozantinib, an inhibitor of MET, VEGFR, and AXL, significantly improved overall survival (OS) and progressionfree survival (PFS) versus placebo in patients with previously treated HCC and is now approved for patients with HCC who have received prior sorafenib. Here we evaluate clinical outcomes based on ALBI grade in the CELESTIAL trial. Methods: 707 patients were randomized 2:1 to receive cabozantinib (60 mg daily) or placebo. Eligible patients had a pathologic diagnosis of HCC, Child-Pugh score A, and ECOG PS≤1. Patients received prior sorafenib and≤2 lines of prior systemic therapy for HCC. ALBI score at baseline was calculated from serum albumin and total bilirubin measured centrally and ALBI grade was determined by the calculated score (Johnson, 2015). Results: At baseline 186 patients (40%) were ALBI grade 1 and 282 patients (60%) were ALBI grade 2 in the cabozantinib arm. One hundred and two patients (43%) were ALBI grade 1 and 133 patients (56%) were ALBI grade 2 in the placebo arm. Two patients in each arm were ALBI grade 3. Patients with ALBI grade 1 had better ECOG PS (61% ECOG 0 & 39% ECOG 1) versus those with ALBI grade 2 (48% ECOG 0 & 52% ECOG 1). In patients with ALBI grade 1, median OS was 17.5 months with cabozantinib versus 11.4 months with placebo (HR 0.63, 95% CI 0.46-0.86). In patients with ALBI grade 2, median OS was 8.0 months with cabozantinib versus 6.4 months with placebo (HR 0.84, 95% CI 0.66-1.06). In patients with ALBI grade 1, median PFS was 6.5 months with cabozantinib versus 1.9 months with placebo (HR 0.42, 95% CI 0.32-0.56) while in patients with ALBI grade 2, median PFS was 3.7 months with cabozantinib versus 1.9 months with placebo (HR 0.46, 95% CI 0.37-0.58). The most common grade 3/4 adverse events in both groups were consistent with those in the overall population. Treatment-related discontinuations in the cabozantinib arm were 12% for patients with ALBI grade 1 and 19% for those with ALBI grade 2. Conclusion: Patients treated with cabozantinib had longer PFS and OS compared to patients receiving placebo, regardless of ALBI grade. Outcomes were generally better in patients with ALBI grade 1 versus 2.