December 19 2024
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,” stated 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. “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.”
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.
Citation
Dawson LA, Winter KA, Knox JJ, et al. Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial. JAMA Oncol. Published online December 19, 2024. doi:10.1001/jamaoncol.2024.5403
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.