The administration of stereotactic body radiation therapy (SBRT) prior to sorafenib may improve outcomes in patients with advanced hepatocellular carcinoma (HCC), according to research presented at the 2023 ASCO Gastrointestinal Cancers Symposium.
In this phase 3 trial, patients who received SBRT and sorafenib had a significant improvement in progression-free survival (PFS), compared with those who received sorafenib alone. A multivariable analysis showed a significant improvement in overall survival (OS) with SBRT as well.
The trial (ClinicalTrials.gov Identifier: NCT01730937) included 177 patients with locally advanced HCC and any degree of vascular invasion who were not candidates for standard therapy. The patients’ median age was 66 (range, 27-84) years. The median tumor volume was 180 cc (interquartile range, 72-409 cc), and the median sum of tumor diameter was 7.8 cm (range, 1-19.1 cm).
Patients were randomly assigned to receive sorafenib alone (n=92) or SBRT followed by sorafenib (n=85). In the monotherapy arm, patients received sorafenib at 400 mg twice daily. In the dual therapy arm, patients received SBRT at 27.5-50 Gy in 5 fractions, followed by sorafenib at 200 mg twice daily for 4 weeks and 400 mg twice daily thereafter.
In the sorafenib monotherapy arm, 3 patients did not ultimately receive sorafenib, and 21% received SBRT after stopping sorafenib. In the dual therapy arm, 12 patients received SBRT without sorafenib, 1 patient did not receive either therapy, and 4 patients did not complete SBRT.
The SBRT arm had a longer median treatment duration than the monotherapy arm (5.1 months and 2.7 months, respectively). The median daily dose of sorafenib was lower in the SBRT arm as well (371 mg and 500 mg, respectively).
The median follow-up was 13.2 months. The median OS was 12.3 months in the monotherapy arm and 15.8 months in the SBRT arm, which trended toward significance (hazard ratio [HR], 0.77; 95% CI, 0.59-1.01; P =.055). The 12-month OS rate was 59% in the SBRT arm and 53% in the monotherapy arm. The 24-month OS rate was 33% and 23%, respectively.
In a multivariable analysis, significant predictors for OS were treatment (HR, 0.72; P =.042), Zubrod performance score (HR, 1.44; P =.003), Child Pugh Score (HR, 1.48; P =.038), extent of macrovascular involvement (HR, 2.34; P <.0001), and clinical M stage (HR, 2.72; P =.013).
The median PFS and time to progression were significantly improved with SBRT. The median PFS was 9.2 months in the SBRT arm and 5.5 months in the monotherapy arm (HR, 0.55; 95% CI, 0.40-0.75; P =.0001). The median time to progression was 18.5 months and 9.5 months, respectively (HR, 0.69; 95% CI, 0.48-0.99; P =.034).
The rate of grade 3 or higher treatment-related adverse events (TRAEs) was 47% in the SBRT arm and 42% in the monotherapy arm. Grade 3 or higher gastrointestinal TRAEs were more common in the SBRT arm than in the monotherapy arm (10% and 7%, respectively), as were grade 3 or higher blood work changes (27% and 19%, respectively). Grade 3 or higher hepatobiliary TRAEs were more common in the monotherapy arm than in the SBRT arm (3% and 1%, respectively).
“In patients with advanced hepatocellular carcinoma, compared to sorafenib alone, SBRT prior to sorafenib improved overall survival, progression-free survival, and time to progression, with no concerning increase in adverse events,” said study presenter Laura A. Dawson, MD, of Princess Margaret Cancer Centre in Toronto, Canada.
“This adds to the body of evidence for the role of external beam radiation, bringing SBRT to our armamentarium of treatment options for patients,” she added.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Dawson LA, Winter KA, Knox JJ, et al. NRG/RTOG 1112: Randomized phase III study of sorafenib vs. stereotactic body radiation therapy (SBRT) followed by sorafenib in hepatocellular carcinoma (HCC). ASCO GI 2023. January 19-21, 2023. Abstract 489.