Cabozantinib shows promising outcomes in advanced HCC
Cabozantinib, an oral inhibitor of multiple tyrosine kinases, significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced hepatocellular carcinoma (HCC) whose disease progressed following sorafenib or other systemic therapies.
In the phase III CELESTIAL trial in 707 patients, the primary endpoint of OS showed a 2.2-month improvement in the cabozantinib vs placebo arm. Median OS was 10.2 months with cabozantinib vs 8 months with placebo (hazard ratio [HR], 0.76; p=0.0049). [ASCO GI 2018, abstract 207]
Median PFS was 5.2 months in the cabozantinib arm vs 1.9 months in the placebo arm (HR, 0.44; p<0.0001).
The study included patients who had received up to two prior lines of systemic therapy for HCC, at least one of which must be sorafenib. The patients had disease progression following at least one prior line of treatment. Thirty-eight percent of patients had hepatitis B, while 24 percent had hepatitis C. Twenty-five percent of patients were enrolled in Asia.
“In patients who had received only sorafenib as prior therapy, median OS was 11.2 months in the cabozantinib arm vs 7.2 months in the placebo arm [HR, 0.70]. In these patients, median PFS was 5.5 months vs 1.9 months [HR, 0.40],” reported investigator Dr Ghassan K. Abou-Alfa of the Memorial Sloan Kettering Cancer Center in New York City, New York, US.
However, the objective response rate was low, at 4 percent in the cabozantinib arm vs 0.4 percent in the placebo arm (p=0.0086). The disease control rate was 64 percent vs 33 percent.
“There was no complete response in either group,” said Abou-Alfa. “Partial response was achieved by 4 percent of patients in the cabozantinib group vs 0.4 percent of patients in the placebo group. Stable disease was observed in 60 percent vs 33 percent of patients, while disease progression occurred in 21 percent vs 55 percent of patients. Fifteen percent of patients in the cabozantinib arm and 11 percent of those in the placebo arm were not evaluable.”
In the study, the most common grade 3/4 adverse events that were more common in the cabozantinib vs placebo arm included hand-foot skin reaction (17 vs 0 percent), hypertension (16 vs 2 percent), elevated aspartate aminotransferase (12 vs 7 percent), fatigue (10 vs 4 percent), and diarrhoea (10 vs 2 percent). The adverse events were consistent with the known safety profile of cabozantinib.
After the study, 25 percent of patients in the cabozantinib arm and 30 percent of those in the placebo arm received subsequent therapy. The median time to subsequent systemic therapy was 6.6 months vs 3.3 months.
“Based on these findings, cabozantinib represents a new treatment option for patients with advanced HCC after prior systemic therapy,” said Abou-Alfa.
Cabozantinib inhibits MET, VEGF and AXL, which are involved in tumour angiogenesis, growth, invasiveness and metastasis, as well as drug resistance. The agent is approved by the US FDA for treatment of metastatic medullary thyroid cancer and advanced renal cell carcinoma.