EASL-Brivanib Improves Time-to-Progression in Patients With HCC, but Fails to Improve Overall Survival

Brivanib Improves Time-to-Progression in Patients With HCC, but Fails to Improve Overall Survival

By Chris Berrie

BARCELONA, Spain -- April 24, 2012 -- Brivanib does not appear to significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib, according to a study presented here at the 47th Annual Meeting of the European Association for the Study of the Liver (EASL).

However, improvements were seen for time-to-progression, disease control rate, and overall response rate, indicating anti-tumour activity of the drug.
HCC is one of the most common cancers worldwide, with patients often showing advanced disease at diagnosis.

“Effective treatments for HCC after sorafenib failure remain an unmet need,” said Josep M. Llovet, MD, Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York, on April 21.
For the study, 395 patients with HCC who had progressed on, or were intolerant to, sorafenib were randomised to receive best supportive care plus placebo (n = 132) or oral brivanib 800 mg/day (n = 263) until disease progression or unacceptable toxicity.

The primary endpoint of overall survival (OS) was not met, with no significant difference between the placebo and brivanib group (8.2 vs 9.4 months; P =.3307).

However, time-to-progression was increased among patients receiving brivanib versus those receiving placebo (4.2 vs 2.7 months; P =.0001).

Median progression-free survival was also improved in patients receiving brivanib (4.1 vs 2.7 months).
The overall response rate was 2% among patients receiving placebo, compared with 12% among patients receiving brivanib (2% vs 12%; P =.0032).

Grades 3 to 5 adverse events were more common in the brivanib arm, and there were more frequent dose reductions due to adverse events.

Patient deaths within 30 days of the last dosing were similar between groups, but 6 deaths were attributed to brivanib by the investigators (encephalopathy [n = 2], liver failure, acidosis, sudden death, coma/cerebral oedema).

Dr. Llovet noted that the alpha-fetoprotein cutoff and portal vein invasion were among the prognostic factors for overall survival, both of which had shown some baseline imbalance between placebo and brivanib (45% vs 52%; 12% vs 25%, respectively).
“Prespecified and exploratory analyses suggested that due to potential imbalances in some prognostic factors, there may have been an underestimate of the treatment effect,” said Dr. Llovet.
Funding for this study was provided by Bristol-Myers Squibb.

[Presentation title: Brivanib Versus Placebo in Patients With Advanced Hepatocellular Carcinoma (HCC) Who Failed or Were Intolerant to Sorafenib: Results From the Phase 3 BRISK-PS Study. Abstract 1398]

Source: DGNews