Hepatocellular carcinoma is the 4th most common malignancy and the 2nd leading cause of tumor death in China, with hepatocellular carcinoma being the most common form of liver cancer. Without treatment, patients with advanced liver cancer usually do not survive more than 6 months.
In 2018, the American Society of Clinical Oncology Gastrointestinal Oncology Symposium published the results of the phase III CELESTIAL trial: compared with placebo, cabozantinib significantly improved the prognosis of patients with advanced hepatocellular carcinoma[2].
The announcement of the results of this phase III CELESTIAL clinical trial is certainly good news for patients with advanced hepatocellular carcinoma. So what kind of drug is cabozantinib?
Cabozantinib is a multi-targeted anti-cancer drug
Cabozantinib is a tumor-targeting drug, a small molecule inhibitor. It is designed to target an oncogenic site at the cellular molecular level, and the drug enters the body to specifically select the oncogenic site, bind, and act in a way that specifically kills tumor cells without affecting normal tissue cells.
Cabozantinib effectively inhibits human hepatocyte growthfactor receptor (MET), alanine aminotransferase, and the receptor targets of vascular endothelial growth factor receptor 1, vascular endothelial growth factor receptor 2, and vascular endothelial growth factor receptor 3[3], all of which are involved in a range of disease-related processes, including tumor angiogenesis, invasion, metastasis, and drug resistance.
Effectiveness of cabozantinib in advanced hepatocellular carcinoma
In this phase III CELESTIAL clinical trial, a total of 707 patients with advanced hepatocellular carcinoma were involved, all of whom had disease progression despite treatment with sorafenib or other systemic therapy.
Patients were randomly assigned in a 2:1 ratio to receive treatment with cabozantinib (60 mg daily) and placebo, and treatment continued until clinical benefit was lost or intolerable toxicity developed.
The primary study endpoint set for the study was overall survival, and secondary endpoints included progression-free survival and objective remission rate.
The trial results showed a median overall survival of 10.2 months in the cabozantinib group compared with 8.0 months in the placebo group, and a 24% reduction in the risk of death in patients on cabozantinib. Median progression-free survival was 5.2 months in the cabozantinib group versus 1.9 months in the placebo group. The objective remission rate was 4% in the cabozantinib group versus 0.4% in the placebo group. The disease control rate was 64% in the cabozantinib group and 33% in the placebo group.
From this, we can see that cabozantinib was superior to placebo for both the primary and secondary study endpoints.
The phase III CELESTIAL clinical trial demonstrated a benefit for advanced hepatocellular carcinoma treated with cabozantinib, and the industry believes that cabozantinib is on track to be approved as a second-line treatment for advanced hepatocellular carcinoma. Although it is only second-line, it is one more option for patients and one more hope.
Cabotinib is, after all, an anti-cancer drug, and the adverse effects of the drug should not be underestimated. Grade 3 and 4 adverse reactions that were observed more frequently in the cabozantinib group in the study included skin reactions in the hands and feet, hypertension, elevated aspartate aminotransferase, fatigue, diarrhea, weakness, and decreased appetite. The incidence of grade 5 adverse drug reactions was higher in the cabozantinib group compared with placebo.
Summary
The investigators of the phase III CELESTIAL study concluded that cabozantinib greatly improved overall and progression-free survival and significantly improved objective remission rates in patients with advanced hepatocellular carcinoma. If approved, cabozantinib may become a new treatment option for patients with advanced hepatocellular carcinoma.