Recent results from the Phase III clinical trial NRG-RTOG 1112 showed that the addition of stereotactic body radiotherapy (SBRT) to systemic sorafenib treatment significantly improved progression-free survival (PFS) and time to progression in patients with locally advanced hepatocellular carcinoma (HCC). compared to sorafenib alone. Furthermore, the addition of SBRT to sorafenib was associated with clinically significant 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 after treatment. Invasion of HCC into the major hepatic vessels, referred to as macrovascular invasion (MVI), is associated with an increased risk of metastases and lower survival. This population has an unmet need for better cancer control and improved survival outcomes. The improved outcomes observed with the addition of SBRT, particularly in patients with MVI, are consistent with previous smaller studies and provide evidence for the efficacy of SBRT in patients with HCC. These results also provide a strong rationale for randomized trials 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 lead author of the NRG-RTOG 1112 manuscript
NRG-RTOG 1112 enrolled 177 eligible patients and stratified patients by performance status, liver function, grade of metastases, and grade of MVI. MVI was observed in 131 of 177 (74%) patients pooled. Patients were randomized to receive SBRT with sorafenib or sorafenib alone. Patients who received 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.
Median OS was 12.3 months in the sorafenib alone arm (90% CI 10.6–14.3) versus 15.8 months in the sorafenib plus SBRT arm (90% CI 11.4–19.2) ( risk ratio [HR] 0.77, 90% CI 0.59–1.01, one-tailed p=0.055).
In addition, median PFS improved from 5.5 months in the sorafenib alone arm (95% CI 3.4–6.3) to 9.2 months in the SBRT plus sorafenib 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 observed in 42% of patients treated with sorafenib and in 47% of patients treated with SBRT and sorafenib (p=0.52). Two treatment-related deaths occurred in the sorafenib-only 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. Improvement in quality of life was seen in 10% of patients receiving the sorafenib treatment arm alone versus 35% of patients in the SBRT with sorafenib treatment arm.
This study was funded by grants 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.
Source:
Journal Reference:
Dawson, LA, et al. (2024). Stereotactic Body Radiotherapy Versus Sorafenib Alone in Hepatocellular Carcinoma. JAMA Oncology. doi.org/10.1001/jamaoncol.2024.5403.
