The median age of participants was 66 years (range, 27-84 years); 41% had hepatitis C, and 19% had hepatitis B or B/C. Additionally, 82% had Barcelona Clinic Liver Cancer stage C disease, and 74% had macrovascular invasion.
The median follow-up was 13.2 months overall and 33.7 months for living patients.
Median overall survival improved from 12.3 months with sorafenib alone to 15.8 months with the addition of SBRT to the regimen (hazard ratio [HR] = 0.77; one-sided P = .0554). A prespecified multivariable analysis showed that the combination therapy resulted in a statistically significant improvement in overall survival after adjustment for confounders (HR, 0.72; P = .042).
Similarly, median PFS also improved from 5.5 months with sorafenib alone to 9.2 months with SBRT and sorafenib (HR = 0.55; two-sided P = .0001).
With regard to safety, gastrointestinal bleeds occurred in 4% of patients in the combination arm, vs. 6% of those in the monotherapy arm. Overall, rates of treatment-related grade 3+ adverse events did not significantly differ between study arms (42% vs. 47%; P = .52). There were three grade 5 events; two in the sorafenib-only group and one in the SBRT/sorafenib group.
The researchers also evaluated quality of life (QoL). “Our hypothesis was that patients treated with SBRT and sorafenib would have improved quality of life 6 months after the start of treatment compared to sorafenib alone,” said Dr. Dawson.
About half (47%) of participants agreed to fill out QoL assessments, but baseline and 6-month data were available for only about 21% of participants. Although the numbers were considered too small to analyze statistically, substantial improvement was seen in the group that received combination therapy. A total of 10% of patients who received sorafenib reported improvement on the FACT-Hep score, vs. 35% of patients who received SBRT/sorafenib.
“As compared to sorafenib, SBRT improved overall survival and progression-free survival, with no observed increase in adverse events in patients with advanced HCC,” concluded Dr. Dawson.
Where does radiation fit?
Invited discussant Laura Goff, MD, associate professor of medicine, Vanderbilt Ingram Cancer Center, Nashville, Tenn., reiterated that SBRT given prior to sorafenib improved outcomes compared to sorafenib alone, and while not definitive, Quality and Outcomes Framework scores appeared to improve at 6 months for the combination arm. “This reassures our concerns about toxicity,” she said.
Dr. Goff pointed out that since the study closed early, owing to changes in standard of care for HCC, the question arises – where does radiation fit in the array of options now available for HCC?
“For one, sorafenib plus SBRT represents an intriguing first-line option for patients who cannot be treated with immunotherapy, such as those who experience a posttransplant recurrence,” Dr. Goff said. “There is also renewed interest in radiation therapy in liver-dominant HCC, and there is active investigation ongoing for a variety of combinations.”
Dr. Dawson reported relationships with Merck and Raysearch. Dr. Goff reported relationships with Agios, ASLAN, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics.
A version of this article first appeared on Medscape.com.