Advanced HCC survival boost with cabozantinib
medwireNews: Patients with previously treated advanced hepatocellular carcinoma (HCC) may derive a survival advantage from treatment with the multikinase inhibitor cabozantinib, CELESTIAL trial results indicate.
Cabozantinib – which targets VEGFR 1, 2, and 3, MET, and AXL – was associated with a significant 24% reduction in the risk for death relative to placebo in the double-blind, phase III trial, reports the team led by Ghassan Abou-Alfa, from the Memorial Sloan Kettering Cancer Center in New York, USA.
The median overall survival times were 10.2 months for the 470 HCC patients who were randomly assigned to receive cabozantinib 60 mg/day and 8.0 months for the 237 patients treated with placebo.
Participants in the cabozantinib group also had significantly longer progression-free survival than those in the placebo group, at a median of 5.2 versus 1.9 months (hazard ratio=0.44), and the objective response rate was also higher with cabozantinib than placebo, at 4% and less than 1%, respectively.
Abou-Alfa and colleagues note that “[a]dverse events were consistent with the known safety profile of cabozantinib,” and “were managed with dose modifications and supportive care.”
Grade 3 or 4 toxicities occurred in 68% of cabozantinib-treated participants and in 36% of their counterparts given placebo, with palmar–plantar erythrodysesthesia (17 vs 0%), hypertension (16 vs 2%), elevated aspartate aminotransferase (12 vs 7%), fatigue (10 vs 4%), and diarrhea (10 vs 2%) the most frequent events.
Six patients in the cabozantinib group experienced a grade 5 treatment-related adverse event, as did one patient in the placebo group.
And dose reductions were required by 62% of participants who received cabozantinib and 13% of those treated with placebo, while the corresponding rates for toxicity-related discontinuation were 16% and 3%.
The trial, which appears in The New England Journal of Medicine, included patients who had received up to two prior systemic regimens for inoperable, advanced HCC. Participants were required to have an ECOG performance status of 0 or 1, and a Child–Pugh score of A.
The researchers explain that “[b]ecause the survival of patients who have hepatocellular carcinoma with Child–Pugh liver disease of class B or worse is determined by liver failure, and it may be impossible to discern any effect of treatment on the cancer, it is justified to exclude these patients from pivotal clinical trials.”
And they conclude: “Thus, as with all other agents approved for treatment of hepatocellular carcinoma, additional studies are required to confirm the safety and efficacy of cabozantinib in patients with more compromised liver function or poorer performance status.”
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