Pivotal Results from Phase 3 Trial Shows Longer Overall Survival with Cabozantinib than with Placebo in Patients with Advanced Liver Cancer


Bottom Line:

New researched published in the New England Journal of Medicine and conducted by Memorial Sloan Kettering researchers offer proof of better treatment options for patients with advanced hepatocellular carcinoma the most common form of liver cancer. The data, originally presented at the 2018 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO-GI) in January 2018, demonstrate that cabozantinib provided a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo.


Cabozantinib in Patients with Advanced and Progressing Hepatocellurlar Carcinoma” published online July 4, 2018 in the New England Journal of Medicine.


MSK’s Ghassan Abou-Alfa, MD, MBA, was the lead and senior corresponding author of this study.


This randomized, double blind, phase III trial evaluated cabozantinib as compared with a placebo in previously treated patients with advanced hepatocellular carcinoma. The trial was conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 707 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017.

Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region and presence of extrahepatic spread and/or macrovascular invasion. No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is overall survival (OS), and secondary endpoints include objective response rate and progression-free survival (PFS).


Among patients with previously treated advanced hepatocellular carcinoma, treated with cabozantinib resulted in longer overall survival and progression free survival than the placebo. Median overall survival was 10.2 months for trial participants who took cabozantinib versus 8.0 months with placebo. Median PFS was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo.

Author Comments:

“Patients with this form of advanced liver cancer have very limited treatment options once their disease progresses following treatment with sorafenib,” said MSK medical oncologist Ghassan K. Abou-Alfa, MD, MBA, and lead investigator on the trial. “These results suggest that, if approved, cabozantinib could become an important addition to the treatment landscape that may help slow disease progression and, critically, improve survival for these patients.”