Higher Baseline AFP Linked to Greater Benefit With Cabozantinib in Hepatocellular Carcinoma
Cabozantinib prolonged survival in relapsed HCC across a range of AFP levels, but a larger treatment benefit was observed with higher baseline AFP.
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Higher baseline serum alpha fetoprotein (AFP) levels were associated with a larger treatment benefit with cabozantinib compared with placebo among patients with relapsed/refractory hepatocellular carcinoma (HCC), according to an analysis of the CELESTIAL trial presented at the 2018 ESMO Congress in Munich, Germany.1
A poor prognosis is associated with high baseline levels of AFP among patients with HCC. In the phase 3 CELESTIAL trial, cabozantinib significantly prolonged overall survival (OS) and progression-free survival (PFS) compared with placebo among patients with previously treated advanced HCC. The purpose of this analysis was to stratify the outcomes of the CELESTIAL trial by baseline AFP levels.
The phase 3 CELESTIAL trial randomly assigned 707 patients with relapsed/refractory HCC 2:1 to receive cabozantinib or placebo. All patients received prior sorafenib and up to 2 lines of systemic treatment. At baseline, all patients had a Child-Pugh score A and an ECOG performance status of 1 or less.
Most patients had a baseline AFP level of at least 20 ng/mL. At baseline, 69% of patients had a baseline AFP level of 20 ng/mL or more, 49% had levels of 200 ng/mL or more, and 41% had levels of 400 ng/mL or more.
Cabozantinib significantly prolonged PFS compared with placebo regardless of baseline AFP levels, with hazard ratios (HRs) ranging from 0.39 to 0.57. The median PFS was 5.5 months and 1.9 months with cabozantinib or placebo, respectively, among patients with an AFP level of less than 400 ng/mL at baseline (HR, 0.47; 95% CI, 0.37-0.60). For patients with an AFP levels greater than or equal to 400 ng/mL at baseline, median PFS was 3.9 and 1.9 months with cabozantinib or placebo, respectively (HR, 0.42; 95% CI, 0.32-0.55).
Median OS was longer with cabozantinib compared with placebo for all patients with a baseline AFP levels greater than or equal to 20 ng/mL. OS was a median 13.9 with cabozantinib compared with 10.3 months with placebo among patients with an AFP less than 400 ng/mL (HR, 0.81; 95% CI, 0.62-1.04). In the AFP greater than or equal to 400 ng/mL cohort, the median OS was 8.5 months compared with 5.2 months with cabozantinib or placebo, respectively (HR, 0.71; 95% CI, 0.54-0.94).
A high baseline AFP level was associated with an increased risk for developing high-grade transaminitis, regardless of treatment with cabozantinib or placebo. Grade 3/4 aspartate aminotransferase elevation was significantly greater with cabozantinib at 8% and 17% compared with placebo at 4% and 11% for patients with an AFP level less than 400 ng/mL or 400 ng/mL or higher, respectively.
The authors concluded that though patients with a range of baseline AFP levels experienced improved PFS and OS, “high AFP levels were associated with a larger treatment benefit with cabozantinib.”
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- Kelley RK, El-Khoueiry AB, Meyer T, et al. 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). Presented at: 2018 ESMO Congress; Munich, Germany: October 19-23, 2018. Abstract 702P.