2018 GI CANCERS SYMPOSIUM: Cabozantinib Demonstrates Significant Overall Survival Benefit in Patients With Previously Treated Advanced HCC
Detailed results of the phase III CELESTIAL trial in patients with previously treated advanced hepatocellular carcinoma (HCC) were presented in a late-breaking oral session by Abou-Alfa et al at the 2018 ASCO Gastrointestinal (GI) Cancers Symposium (Abstract 207).
Study Findings
In CELESTIAL, cabozantinib (Cabometyx) provided a statistically significant and clinically meaningful improvement vs placebo in overall survival, the trial’s primary endpoint, at the planned second interim analysis (prespecified P ≤ .021) for the population of patients receiving second- and third-line treatment enrolled in this study. Median overall survival was 10.2 months with cabozantinib vs 8.0 months with placebo (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.63–0.92; P = .0049). Median progression-free survival was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo (HR = 0.44, 95% CI = 0.36–0.52; P < .0001).
Objective response rates per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were 4% with cabozantinib and 0.4% with placebo (P = .0086). Disease control (partial response or stable disease) was achieved by 64% of the cabozantinib group, compared with 33% of the placebo group.
In a subgroup analysis of patients whose only prior therapy for advanced HCC was sorafenib (Nexavar, 70% of patients in the study), median overall survival was 11.3 months with cabozantinib vs 7.2 months with placebo (HR = 0.70, 95% CI = 0.55–0.88). Median progression-free survival in the subgroup was 5.5 months with cabozantinib vs 1.9 months with placebo (HR = 0.40, 95% CI = 0.32–0.50). Adverse events were consistent with the known safety profile of cabozantinib.
Safety and Adverse Events
The most common (≥ 10%) grade 3 or 4 adverse events in the cabozantinib group compared to the placebo group were palmar-plantar erythrodysesthesia (17% vs 0%), hypertension (16% vs 2%), increased aspartate aminotransferase (12% vs 7%), fatigue (10% vs 4%), and diarrhea (10% vs 2%). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism, and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure). About 16% of patients in the cabozantinib arm and 3% of patients in the placebo arm discontinued treatment due to treatment-related adverse events.
Ghassan K. Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center and lead investigator for the CELESTIAL trial, said, “Patients with advanced HCC often have a poor prognosis and limited treatment options following prior systemic therapy. The clinically significant benefits in both overall survival and progression-free survival shown in the CELESTIAL trial suggest that, if approved, cabozantinib could become an important addition to the treatment landscape for these patients.”
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