ON JANUARY 14, 2019, the U.S. Food and Drug Administration (FDA) approved cabozantinib, an orally available receptor tyrosine kinase inhibitor, for patients with hepatocellular carcinoma who have been previously treated with sorafenib. The FDA’s approval was based on the results of the phase III CELESTIAL trial.1
Cabozantinib improved the median overall survival to 10.2 months vs 8 months with placebo in patients with hepatocellular cancer who had disease progression after at least 1 line of systemic therapy. The study was stopped early because of benefit. These data from the CELESTIAL trial were originally presented at the 2018 Gastrointestinal Cancers Symposium and were later published in The New England Journal of Medicine.2
Ghassan K. Abou-Alfa, MD
At the 2019 Gastrointestinal Cancers Symposium, Ghassan K. Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center, and lead investigator of the CELESTIAL trial, presented a post hoc analysis on the incremental quality-adjusted life-years accrued with cabozantinib in patients with advanced hepatocellular carcinoma in the trial.
Impact on Quality of Life
FOLLOWING THE IMPROVEMENT in progression-free and overall survival demonstrated in the CELESTIAL trial, investigators sought to determine the impact of cabozantinib on quality of life in the study population of patients with hepatocellular carcinoma. They used a five-dimensional, five-level quality-of-life survey (EQ-5D-5L) to evaluate health utility, which included patient-reported mobility, self-care, activities of daily living, pain or discomfort, and anxiety and depression. Overall, the survey was completed by 82% to 10 0% of patients at incremental time points following therapy with cabozantinib.
At 50 days postrandomization there was a reduction in health utility reported by patients receiving cabozantinib vs placebo. At subsequent time points, the investigators reported that patients receiving cabozantinib showed a more favorable benefit in health utility vs patients receiving placebo, and this benefit continued to increase with time.
Study limitations included a short follow-up and a high proportion of censored patients because the trial was stopped early. Further, the analysis did not include mortality. The investigators summarized that cabozantinib was associated with an initial, small reduction in health utility compared with placebo. As treatment continued, they reported there was a clinically and statistically significant increase in health utility in favor of cabozantinib vs placebo.
In conclusion, the investigators reported that cabozantinib improved progression-free survival and overall survival as reported in the phase III CELESTIAL trial. Based on the post hoc analysis, they noted that cabozantinib also resulted in improved quality of life in patients in the CELESTIAL trial as determined by the EU-EQ-5L questionnaire. ■
DISCLOSURE: Dr. Abou-Alfa has served in a consulting and advisory role for Exelixis, Bayer, and Bristol-Myers Squibb.
1. Abou-Alfa GK, Mollon P, Meyer T, et al: Quality-adjusted life years accrued with cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial. 2019 Gastrointestinal Cancers Symposium. Abstract 207. Presented January 18, 2019.
2. Abou-Alfa GK, Meyer T, Cheng AL, et al: Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 379:54-63, 2018.