The study, the first National Cancer Institute-sponsored multicooperative group hepatobiliary cancer phase 3 study, sought to determine if doxorubicin plus sorafenib improved survival compared with sorafenib alone.
Patients who had no prior systemic therapy scored Child-Pugh A were randomly assigned to receive doxorubicin 60 mg/m2 intravenously every 21 days plus sorafenib 400 mg orally twice daily or sorafenib alone. Those with a baseline bilirubin greater than 1.2 were offered half doses of both doxorubicin and sorafenib.
The study was halted after accrual of 346 patients — 173 on each of the doxorubicin plus sorafenib and sorafenib arms — when a futility boundary was crossed at a planned interim analysis.
With 130 events in the doxorubicin plus sorafenib arm and 123 in the sorafenib arm, median overall survival was 8.9 months for doxorubicin plus sorafenib, and 10.5 months for sorafenib alone (HR, 1.06; 95% CI, 0.8-1.4; P = .24).
Median progression-free survival was 4.0 months in the doxorubicin plus sorafenib arm and 3.9 months in the sorafenib alone arm (HR, 0.90; 95% CI, 0.72-1.2; P = .98).
A total of 12 deaths occurred on the study that were possibly related to treatment, 8 in the doxorubicin plus sorafenib arm: cardiac (2), failure to thrive (1), infection (2), hepatic failure (2), and not otherwise specified (1), as were 4 deaths in the sorafenib arm: hepatic failure (1), malignancy (1), thromboembolic (1), and not otherwise specified (1).
Grade 3 or greater hematologic adverse events occurred in 58% of patients on doxorubicin plus sorafenib and 1% of patients on sorafenib. A total of 7% of patients on the doxorubicin plus sorafenib arm had grade 3/4 ejection fraction/left ventricular systolic dysfunction. Nonhematologic adverse events were comparable and included fatigue, hypertension, and hand-foot syndrome.
“A series of scientific correlates await reporting,” Dr. Abou-Alfa said.
1. Abou-Alfa GK, Niedzwieski D, Knox JJ, et al. Phase III randomized study of sorafenib plus doxorubicin versus sorafenib in patients with advanced hepatocellular carcinoma (HCC): CALGB 80802 (Alliance). Oral presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.