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.”
REFERENCE
Savona Discusses First-Line JAK Inhibition for Patients With Myelofibrosis at Risk of Anemia
April 17th 2024During a Case-Based Roundtable® event, Michael Savona, MD, and participants discussed the case of a patient with myelofibrosis and moderate anemia receiving JAK inhibitor therapy.
Read More
Biomarker Testing Paves the Way for Better Targeted Therapies in NSCLC
April 16th 2024At a live virtual event, Edward S. Kim, MD, MBA, discussed the evolving landscape of biomarker testing before making treatment decisions for patients with early-stage non–small cell lung cancer (NSCLC).
Read More
Creating Solutions for a 'Continual State of Transition' in Cancer Care
April 15th 2024In a Peers & Perspectives in Oncology feature article, we focus on the importance of the transition-of-care process for patients with cancer as they move from the inpatient to outpatient setting, as well as between lines of therapy with comments from Marc J. Braunstein, MD, PhD, and Michael Shusterman, MD.
Read More