Personalized stereotactic body radiation therapy (SBRT) followed by sorafenib improves survival in hepatocellular carcinoma (HCC) patients, with no observed increase in adverse events and a strong suggestion for improved quality of life over sorafenib alone.
In the randomized Phase III NRG/RTOG-1112 study, patients with HCC treated with SBRT and sorafenib had improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib alone, reported lead author Laura A. Dawson, MD, Professor in the Department of Radiation Oncology at the Princess Margaret Cancer Centre in Toronto, Canada, at the 2023 ASCO Gastrointestinal Cancers Symposium (Abstract 489).
"External beam radiation therapy is an effective therapy in the treatment of HCC that should benefit many patients from around the world in the future, especially patients with macrovascular invasion who previously had limited treatment options," Dawson noted. "Stereotactic body radiation therapy should be included as a standard treatment option for these patients, especially those who have planned to be treated with tyrosine kinase inhibitors or those who are not candidates for or who have progression or intolerance to systemic therapies."
Study Details
Patients in the study were randomly assigned to either sorafenib 400 mg twice daily or SBRT (27.5-50 Gy in 5 fractions) followed by sorafenib 200 mg twice daily, increased to 400 mg twice daily after 28 days. Radiation therapy was personalized with individualized doses.
Researchers originally planned to enroll 292 patients, but the study was closed early in March 2021 due to the change in systemic standard of care with the IMbrave 150 study, where immunotherapy became systemic standard of care, not sorafenib. There was amendment to the statistics that were based on an event analysis with the same expected benefit of radiotherapy, but a reduction in power from 80 percent to 65 percent.
A total of 193 patients were enrolled from 23 sites and 177 eligible patients, median age 66 years, were randomly assigned to sorafenib (92 patients) or SBRT and sorafenib (85 patients). There was good balance between the two arms, Dawson said. The majority of patients were male, about 50 percent had performance status 1 or 2, 40 percent had hepatitis C, and 82 percent had Barcelona Clinic Liver Cancer Stage C. Three-quarters of the patients had macrovascular invasion, mostly involving large vessels.
Results show the median OS was 15.8 months with SBRT plus sorafenib versus 12.3 months with sorafenib alone (HR: 0.77) and median PFS was 9.2 months with SBRT plus sorafenib compared with 5.5 months in those treated with sorafenib alone (HR: 0.55). In a preplanned multivariable analysis considering other important factors, including performance status, M stage, Child-Pugh score, and degree of macrovascular involvement, the addition of SBRT was statistically associated with improved OS (HR: 0.73).
For the most part, treatment was tolerated, Dawson noted. In the sorafenib arm, three patients ended up not receiving sorafenib, and 21 percent went on to receive radiotherapy after sorafenib discontinuation. In the SBRT arm, 12 patients did not go on to receive sorafenib after SBRT; 94 percent received the SBRT as planned.
Adverse events from any cause were similar in both arms, but "three-quarters of patients had Grade 3 or higher adverse events likely due to the locally advanced nature of these cancers that cause sequelae. Specifically, the gastrointestinal bleeds that were seen were similar in both arms. And when looking at serious adverse events related to treatment, they were again similar in both arms-42 percent in the sorafenib arm, 47 percent in the SBRT and sorafenib arm," said Dawson. She noted that Grade 4 and 5 events were higher in the SBRT arm. There was a slight increase in gastrointestinal toxicities with the addition of SBRT, and they tended to be Grade 3 toxicities due to abdominal radiotherapy or transient blood work changes.
In a quality-of-life assessment, only 21 percent of patients filled out questionnaires at baseline and 6 months, and these numbers were considered too small to analyze statistically. However, among these patients, 35 percent reported improved quality of life at 6 months with SBRT versus 10 percent in those treated with sorafenib alone. Also, more patients reported a decline in their quality of life at 6 months in the sorafenib arm versus the sorafenib and SBRT arm.
"[For] patients with advanced HCC compared to sorafenib alone, SBRT prior to sorafenib improved OS, PFS, and time to progression with no concerning increase in adverse events," Dawson noted. "There's a strong suggestion for improved quality of life at 6 months with the addition of SBRT. This adds to the body of evidence for the role of external beam radiation bringing SBRT to the armamentarium of treatment options for patients, particularly in those patients with locally advanced HCC and macrovascular invasion, especially if they are treated with tyrosine kinase inhibitors."
Mark L. Fuerst is a contributing writer.