Upfront treatment with the combination of doxorubicin and sorafenib did not improve overall survival compared with sorafenib alone for patients with advanced hepatocellular carcinoma .
The median OS with sorafenib alone was 10.5 months compared with 8.9 months with the combination (HR, 1.06; 95% CI, 0.8-1.4;P= .24). The median progression-free survival (PFS) was 3.9 months with sorafenib alone versus 4 months with the combination (HR, 0.9; 95% CI, 0.72-1.2;P= .98). Based on the lack of benefit, the study was halted early, after an interim analysis.
“Median OS with sorafenib was comparable to historic controls at 10.5 months. The combination showed a median survival of close to 9 months, this showed that additional doxorubicin did not add anything, and as such, this study is reported as negative,” said lead investigator Ghassan K. Abou-Alfa, MD, medical oncologist, Memorial Sloan Kettering Cancer Center.
In the CALGB 80802 trial, 356 patients with advanced, unresectable HCC were randomized to receive 6 cycles of doxorubicin plus sorafenib (n = 180) or sorafenib alone (n = 176). Doxorubicin was administered at 60 mg/m2 every 21 days. Sorafenib was administered at 400 mg twice daily in each arm.
The median age of patients was 62 years and the majority were male (86%). Most patients had AJCC stage IV disease (61%) and the Child-Pugh grade was A. AFP levels were above normal for 87% and 81% of those in the combination and single-agent arms, respectively.
Hepatitis B infection was noted in 16% of patients, and 34% of patients had hepatitis C virus infection. Both hepatitis viruses infected 6% and 4% of patients, in the combination and single-agent arms, respectively.
Treatment-related grade ≥3 adverse events (AEs) were more common with the combination. The most common grade ≥3 AEs with the combination and single-agent, respectively, were fatigue (10% vs 7%), hypertension (3% vs 13%), leukopenia (11% vs 0%), neutropenia (33% vs 0%), thrombocytopenia (14% vs 1%), and hand-foot skin reaction (10% vs 14%). Additionally, 4.3% of those in the combination arm experienced grade ≥3 cardiac toxicity.
The phase III study was based on promising early data from a phase II trial. In this study, doxorubicin plus sorafenib demonstrated a median OS of 13.7 months compared with 6.5 months with doxorubicin alone (P= .006). These findings of 80802 further emphasize the importance of phase III results when selecting therapy for patients with HCC.
“CALGB 80802 was the first NCI-sponsored multicooperative group hepatobiliary cancer phase III study,” said Abou- Alfa. “A series of scientific correlates await reporting.”