GHASSAN K. ABOU-ALFA, M.D., reports on findings from the CELESTIAL trial. - PHOTO BY ASCO/TODD BUCHANAN 2018
TREATMENT WITH THE TARGETED drug Cabometyx (cabozantinib), which inhibits the cancer-driving MET, VEGFR2 and other growth factor receptors, improved median overall survival (OS) by 2.2 months compared with placebo for patients with previously treated advanced liver cancer, according to findings from the phase 3 CELESTIAL trial.
In the double-blind trial, median OS with Cabometyx was 10.2 months compared with 8 months with placebo. Median progression-free survival (PFS) with the multikinase inhibitor was 5.2 months compared with 1.9 months for placebo.
Based on findings from the CELESTIAL trial, the drug’s developer, Exelixis, plans to submit a supplemental new drug application to the Food & Drug Administration before the end of the year’s first quarter. The drug is already approved as a treatment for patients with renal cell carcinoma and medullary thyroid cancer.
“Patients with advanced hepatocellular carcinoma often have a poor prognosis and limited treatment options following prior systemic therapy,” lead investigator Ghassan K. Abou-Alfa, M.D., of Memorial Sloan Kettering Cancer Center, in New York City, said in a statement. “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.”
In the trial, 707 patients were randomized in a 2-to-1 ratio to receive Cabometyx or placebo. The objective response rate was 4 percent with Cabometyx compared with 0.4 percent with placebo. When including those with stable disease, the disease control rate with the drug was 64 percent compared with 33 percent for placebo. Those with limited previous treatment had the best results.
More patients discontinued therapy due to treatment-related side effects with Cabometyx compared with placebo (16 percent versus 3 percent). The most common serious or severe side effects with Cabometyx versus placebo, all affecting 17 percent of patients or less, were hand-foot syndrome, hypertension, increased markers in blood that could indicate liver damage, fatigue and diarrhea.
There was a higher incidence of deadly side effects in the Cabometyx arm compared with placebo (six versus one).