The addition of doxorubicin to sorafenib led to higher toxicity and did not improve overall or progression-free survival in patients with advanced hepatocellular carcinoma (HCC), a study presented at the 2016 Gastrointestinal Cancers Symposium in San Francisco, CA, has shown.1

Because an exploratory analysis of a randomized phase 2 study in patients with HCC comparing doxorubicin alone to doxorubicin plus sorafenib demonstrated a significant improve in overall survival with doxorubicin and sorafenib, researchers sought to conduct a pivotal sorafenib trial to assess if doxorubicin plus sorafenib improved survival compared with the tyrosine kinase inhibitor (TKI) alone.

For the study, researchers enrolled 346 patients with histologically proven advanced HCC who had no prior systemic therapy and were Child-Pugh A.

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Participants were randomly assigned to receive doxorubicin 60 mg/m2 intravenously every 21 days plus sorafenib 400 mg orally twice daily or sorafenib alone. Patients could receive up to 360 mg/m2 and those with a bilirubin level 1.3 times normal or higher received half doses of doxorubicin and sorafenib.

Results showed that median overall survival was 9.3 months (95% CI, 7.1 – 12.9) for the combination compared with 10.5 months (95% CI, 7.3 – 14.3) for sorafenib alone (HR, 1.06; 95% CI, 0.8 – 1.4). The median overall survival with sorafenib alone is consistent with previous reports.

Researchers found that median progression-free survival was 3.6 months (95% CI, 2.8 – 4.6) and 3.2 months (95% CI, 2.3 – 4.1), respectively (HR, 0.90; 95% CI, 0.72 – 1.2).

In regard to safety, there were 18 deaths in the combination arm and 20 deaths in the sorafenib alone arm, of which 8 and 3, respectively, were at least possibly related to treatment.

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A total of 37.8% of patients receiving doxorubicin plus sorafenib experienced grade 3 or 4 hematologic adverse events compared with 8.1% of those receiving sorafenib; however, the rate of non-hematologic adverse events were similar between the 2 arms (63.6% vs 61.5%, respectively).


  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). J Clin Oncol. 2016;34(suppl 4S; abstr 192).