Outcomes by prior transarterial chemoembolization (TACE) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC)

Abstract

Background: Pts with HCC and localized disease commonly receive treatment with TACE but often progress and require systemic therapy. In the CELESTIAL trial (NCT01908426), C, an inhibitor of MET, VEGFR, and AXL, improved overall survival (OS) and progression‐free survival (PFS) vs P in previously treated pts with advanced HCC. Median OS was 10.2 mo for C vs 8.0mo for P (HR 0.76, 95% CI 0.63‐0.92; p=0.0049), and median PFS was 5.2 mo for C vs 1.9 mo for P (HR 0.44, 95% CI 0.36‐ 0.52; p<0.0001) (Abou‐Alfa, JCO 2018). Here, outcomes were analyzed for pts who received prior TACE. Methods: 707 pts were randomized 2:1 to receive C (60 mg qd) or P stratified by disease etiology, geographic region, and extent of disease. Eligible pts had pathologic diagnosis of HCC, Child‐Pugh score A, and ECOG PS≤1. Pts must have received prior sorafenib and could have received up to two lines of prior systemic therapy for HCC. Outcomes were analyzed by number of prior TACE treatments (0,≥1, 1‐2, ≥3). Results: Overall, 203 (43%) pts in the C arm and 111 (47%) pts in the P arm had received prior TACE with a median of 2 and 3 treatments, respectively. For pts who received TACE, 54% received 1‐2 treatments and 46% received ≥3. 61% of pts enrolled in Asia, 39% in Europe, and 37% in North America received prior TACE. For pts who received prior TACE vs no TACE, 67% vs 76% received 1 prior systemic regimen and 32%vs 23%received 2. C was associated with improvedOS and PFS vs P irrespective of prior TACE treatment (Table).Median OS was 11.4mo for C vs 8.6mo for P in pts with prior TACE and 9.5mo for C vs 7.2mo for P in pts with no prior TACE. Grade 3/4 adverse events were similar for pts with and without prior TACE in both arms. Conclusions: C improved OS and PFS compared with P in pts with previously treated advanced HCC irrespective of whether they had received prior TACE. (Table Presented).