SAN FRANCISCO – , according to new findings.
The use of SBRT in this setting improved both overall survival and progression-free survival (PFS). There was no increase in adverse events with the addition of SBRT, and results trended toward a quality-of-life benefit at 6 months.
“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 those with locally advanced HCC and macrovascular invasion, especially if they are treated with tyrosine kinase inhibitors [TKIs],” said lead study author Laura A. Dawson, MD, a clinician scientist at the Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto.
Dr. Dawson presented the findings at the ASCO Gastrointestinal Cancers Symposium 2023.
Approached for an outside comment, Mary Feng, MD, professor of radiation oncology at the University of California, San Francisco, said, “This study is really groundbreaking.”
She added that the investigators should be congratulated for executing this ambitious study with worldwide enrollment for a serious disease.
“There are very few studies demonstrating an overall survival benefit from radiation or any local control modality,” she told this news organization. She suggested that the survival benefit seen in this trial was “likely due to the high percentage of patients (74%) with macrovascular invasion, who stand to benefit the most from treatment.
“This study has established the standard of adding SBRT to patients who are treated with TKIs and raises the question of whether adding SBRT to immunotherapy would also result in a survival benefit. This next question must also be tested in a prospective clinical trial,” she said.
At the study’s inception, sorafenib was the standard of care for patients who were unable to undergo surgery, ablation, and/or transarterial chemoembolization (TACE). Dr. Dawson explained that sorafenib had been shown to improve median overall survival, although there was less benefit if macrovascular invasion was present.
“Integrating radiation strategies in HCC management has been a key question over the past few decades,” she said.
In the current study, Dr. Dawson and colleagues added SBRT to sorafenib. The cohort included 177 patients with new or recurrent HCC who were not candidates for surgery, ablation, or TACE. They were randomly assigned to receive either sorafenib 400 mg twice daily or to SBRT (27.5-50 Gy in five fractions) followed by sorafenib 200 mg twice daily; the dosage was then increased to 400 mg twice daily after 28 days.
SBRT improves outcomes
The original plan was to enroll 292 participants, but accrual closed early when the standard of care for systemic treatment of HCC changed following the results of the phase 3 IMbrave150 trial, which showed the superiority of atezolizumab plus bevacizumab as frontline therapy for locally advanced or metastatic HCC. The closure of accrual was agreed upon by the investigators and the data safety monitoring committee, and their statistical analysis plan was revised accordingly. The study became time driven rather than event driven, she noted. This resulted in a decrease from 80% power to 65% power.