Patients with hepatocellular carcinoma (HCC) previously treated with sorafenib have significantly improved overall survival (OS) and progression-free survival (PFS) rates when treated with cabozantinib compared with placebo, according to data being presented at the 2018 Gastrointestinal Cancers Symposium in San Francisco, California.
For the double-blind phase 3 CELESTIAL study (ClinicalTrials.gov Identifier: NCT01908426), researchers randomly assigned 707 patients with advanced HCC to receive oral cabozantinib 60 mg once daily or placebo; 470 and 237 patients were assigned to the cabozantinib and placebo arms, respectively. Eligible patients were previously treated with sorafenib, had disease progression after no more than 2 lines of systemic therapy, and were unamenable to curative therapy.
At the time of data analysis, 484 (68.4%) enrolled patients had died (317 [67.4%] patients in the cabozantinib arm and 167 [70.4%] patients in the placebo arm).
Median OS was 10.2 months among patients in the cabozantinib arm vs 8.0 months for patients in the placebo arm (hazard ratio [HR], 0.76; 95% CI, 0.63-0.92; P =.0049), and median PFS was 5.2 months vs 1.9 months, respectively (HR, 0.44; 95% CI, 0.36-0.52; P <.001). The overall response rate was 4.0% in the cabozantinib arm vs 0.4% in the placebo arm (P =.0086).
The most frequently reported grade 3 to 4 adverse events — which occurred at a higher rate in the cabozantinib arm — included hand-foot-skin reactions, hypertension, elevated aspartate aminotransferase, fatigue, and diarrhea.
The authors concluded that “[cabozantinib] significantly improved OS and PFS vs [placebo] in previously treated patients with advanced HCC. Adverse events were consistent with the known safety profile of [cabozantinib].”
1. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: Results from the randomized phase III CELESTIAL trial. Oral presentation at: 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA.