Cabozantinib (Cabometyx, Exelixis, Inc./Ipsen) improved overall and progression-free survival among previously treated liver cancer patients in the pivotal phase 3 CELESTIAL trial, according to results being presented at the 2018 ASCO-GI Symposium in San Francisco.
At the planned second interim analysis for the second- and third-line advanced hepatocellular carcinoma (HCC) patients in this study, median overall survival (OS) was 10.2 months with cabozantinib versus 8.0 months with placebo (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63–0.92; P = 0.0049). Median progression-free survival (PFS) 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 < 0.0001). Objective response rates per RECIST 1.1 were 4% with cabozantinib and 0.4% with placebo (P = 0.0086). 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 (70% of patients in the study), median OS was 11.3 months with cabozantinib versus 7.2 months with placebo (HR, 0.70; 95% CI, 0.55–0.88). Median PFS in the subgroup was 5.5 months with cabozantinib versus 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.
“Patients with advanced hepatocellular carcinoma often have a poor prognosis and limited treatment options following prior systemic therapy,” said Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center, New York, and lead investigator on CELESTIAL. “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.”
The FDA has approved cabozantinib for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy. Exelixis expects to submit a supplemental new drug application to the FDA for cabozantinib in the first quarter of 2018.
Source: Exelixis; January 16, 2018.