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No survival benefit from brivanib for patients with HCC
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Brivanib did not improve survival among patients with hepatocellular carcinoma who underwent transcatheter arterial chemoembolization in a study presented at the International Liver Cancer Association Annual Conference in Washington, DC.
In a double blind international study, patients with intermediate-state HCC were randomly assigned to 800 mg brivanib or placebo daily. Overall survival (OS) was the primary endpoint, with safety, time to disease progression (TTDP), rate of transcatheter arterial chemoembolization (TACE) sessions and time to extrahepatic spread or vascular invasion (TTES/VI) the secondary endpoints.
“TACE has been shown to prolong survival in intermediate HCC patients; however, post-TACE recurrence is high,” the researchers wrote. “Adding antiangiogenic therapy to TACE has the potential to reduce TACE sessions, delay post-TACE recurrence and improve survival.”
The study, which initially included 870 patients, was terminated early after phase 3 studies did not meet the primary endpoint. At termination, randomly assigned brivanib (n=249) and placebo (n=253) patients had median treatment durations of 6 months and 6.6 months, respectively.
Treated patients did not experience improved OS (median 26.4 months vs. 26.1 months; HR=0.9; 95% CI, 0.66-1.23) or median TTDP (10.9 months vs. 12 months; HR=0.94; 95% CI, 0.72-1.22). Median time to radiographic progression was significantly higher (8.4 months vs. 4.9 months; HR=0.61; 95% CI, 0.48-0.77) for the brivanib arm, while placebo recipients had a greater rate of additional TACE after the initial session (median 1 vs. 0; HR=0.72; 95% CI, 0.61-0.86). TTES/VI was not reached among brivanib patients; median levels in placebo patients occurred at 24.9 months (HR=0.64; 95% CI, 0.45-0.9).
More than 20% of brivanib recipients experienced adverse events including diarrhea, decreased appetite, hand-foot syndrome, hypertension, hypothyroidism, hyponatremia, hypoalbuminemia, proteinuria and thrombocytopenia.
“At early termination, the study did not meet its primary objective of OS improvement,” the researchers wrote. “Secondary and exploratory outcomes supported the biologic activity of brivanib in unresectable HCC. The results in this early-stage HCC population need to be interpreted in the context of early trial termination and unblinding.”
Disclosure: The researchers report numerous financial disclosures.
For more information:
Kudo M. O-022: A Randomized, Double-Blind, Multicenter Phase 3 Study of Brivanib Versus Placebo as Adjuvant Therapy to Trans-Arterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma: Initial Results. Presented at: The International Liver Cancer Association Annual Conference 2013; Sept. 13-15, Washington, DC.