The addition of stereotactic body radiotherapy (SBRT) to systemic therapy with sorafenib may improve progression-free survival and time-to-progression in patients with locally advanced hepatocellular carcinoma compared with sorafenib alone, according to a novel study published by Dawson et al in JAMA Oncology.
Background
“Typically, patients treated with systemic therapy for locally advanced hepatocellular carcinoma [experience cancer recurrence] within the liver following treatment. Invasion of [hepatocellular carcinoma] into the large hepatic vessels, referred to as macrovascular invasion, is associated with increased risk of metastases and lower survival. This population has an unmet need to better control cancer and improve survival outcomes,” stressed lead study author Laura A. Dawson, MD, Professor and Chair of the Department of Radiation Oncology at Temerty Medicine at the University of Toronto and a radiation oncologist at the Princess Margaret Cancer Centre at the University Health Network.
Study Methods and Results
In the phase III NRG-RTOG 1112 clinical trial, researchers recruited 177 eligible patients and stratified them by performance status, liver function, degree of metastases, and degree of macrovascular invasion. They noted that macrovascular invasion was observed in 74% (n = 131/177) of the patients. The researchers then randomly assigned the patients to receive either 27.5 to 50 Gy of SBRT in 5 fractions plus sorafenib or sorafenib alone. The primary endpoint of the trial was overall survival, and the secondary endpoints included progression-free survival, adverse events, and quality of life.
The researchers found that the addition of SBRT to sorafenib was associated with clinically important improvements in overall survival. The median overall survival was 12.3 months in the sorafenib alone group (90% confidence interval [CI] = 10.6–14.3) vs 15.8 months in the combination treatment group (90% CI = 11.4–19.2; hazard ratio [HR] = 0.77, 90% CI = 0.59–1.01, one-sided P = .055).
Additionally, median progression-free was improved from 5.5 months in the sorafenib alone group (95% CI = 3.4–6.3) to 9.2 months in the SBRT plus sorafenib group (95% CI = 7.5–11.9; HR = 0.55, 95% CI = 0.40–0.75, two-sided P < .001).
After a follow-up of 6 months, quality of life also improved with the addition of SRBT. Quality-of-life improvement was seen in 10% of the patients in the sorafenib alone group compared with 35% of those in the SBRT plus sorafenib group.
Grade 3 or greater adverse events were seen in 42% of the patients who received sorafenib alone and 47% of the patients who received SBRT plus sorafenib (P = .52). Two treatment-related deaths occurred in the sorafenib alone group vs one in the SBRT plus sorafenib group.
Conclusions
“The improved outcomes observed with the addition of SBRT, particularly in patients with [macrovascular invasion], are consistent with prior smaller studies and provide evidence for the efficacy of SBRT in patients with [hepatocellular carcinoma]. These results also provide strong rationale for randomized studies of SBRT combined with immunotherapy for patients with [hepatocellular carcinoma] and [macrovascular invasion], which are planned,” Dr. Dawson concluded.
Disclosure: The research in this study was funded by the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.
