Adding SBRT to sorafenib improves survival in hepatocellular carcinoma patients

Recent results from the Phase III NRG-RTOG 1112 clinical study showed that the addition of stereotactic body radiotherapy (SBRT) to systemic therapy with sorafenib significantly improved progression-free survival (PFS) and time-to-progression in patients with locally advanced hepatocellular carcinoma (HCC) when compared to sorafenib alone. Furthermore, the addition of SBRT to sorafenib was associated with clinically important improvements in overall survival (OS) for patients with locally advanced HCC. These results were recently published in JAMA Oncology. The trial was funded by the National Cancer Institute, National Institutes of Health.

Typically, patients treated with systemic therapy for locally advanced hepatocellular carcinoma recur within the liver following treatment. Invasion of HCC into the large hepatic vessels, referred to as macrovascular invasion (MVI), is associated with increased risk of metastases and lower survival. This population has an unmet need to better control cancer and improve survival outcomes. The improved outcomes observed with the addition of SBRT, particularly in patients with MVI, are consistent with prior smaller studies and provide evidence for the efficacy of SBRT in patients with HCC. These results also provide strong rationale for randomized studies of SBRT combined with immunotherapy for patients with HCC and MVI, which are planned.”

Laura A. Dawson MD, Professor and Chair of the Department of Radiation Oncology, Temerty Medicine, University of Toronto, radiation oncologist at the Princess Margaret Cancer Centre, University Health Network, and the lead author of the NRG-RTOG 1112 manuscript

NRG-RTOG 1112 accrued 177 eligible patients and stratified patients by performance status, liver function, degree of metastases, and degree of MVI. MVI was seen in 131 out 177 (74%) of patients accrued. Patients were randomly assigned to receive either SBRT with sorafenib or sorafenib alone. Patients receiving SBRT received 27.5 to 50 Gy in 5 fractions. The primary endpoint of this study was OS; secondary endpoints included PFS, adverse events, and quality of life.

The median OS was 12.3 months on the sorafenib alone treatment arm (90% CI 10.6–14.3) versus 15.8 months on the sorafenib with SBRT treatment arm (90% CI 11.4–19.2) (hazard ratio [HR] 0.77, 90% CI 0.59–1.01, 1-sided p=0.055).

Additionally, median PFS was improved from 5.5 months on the sorafenib alone treatment arm (95% CI 3.4–6.3) to 9.2 months on the SBRT with sorafenib treatment arm (7.5–11.9) (HR, 0.55, 95% CI 0.40–0.75, 2-sided p<0.001). Grade 3 or greater adverse events were seen in 42% of the patients treated with sorafenib and 47% for the patients treated with SBRT and sorafenib (p=0.52). Two treatment-related deaths occurred in the sorafenib alone treatment arm versus one treatment-related death in the SBRT and sorafenib treatment arm.

Quality of life at 6 months was also improved with the addition of SRBT. Quality of life improvement was seen in 10% of patients who were on the sorafenib alone treatment arm versus 35% of patients on the SBRT with sorafenib treatment arm.

This study was funded by U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), and U24CA180803 (IROC) from the National Cancer Institute (NCI), part of the National Institutes of Health.