Adding stereotactic body radiation therapy (SBRT) to sorafenib improves outcomes in patients with advanced hepatocellular carcinoma (HCC), according to a phase 3 trial presented at the 2022 ASTRO Annual Meeting.

Patients who received SBRT had superior overall survival (OS), progression-free survival (PFS), and time to progression (TTP), researchers found.

“SBRT should be a standard treatment option in the toolkit of treatments for patients with hepatocellular carcinoma, especially those with macrovascular invasion who really are in desperate need of improved treatments,” said study presenter Laura A. Dawson, MD, of Princess Margaret Cancer Center in Toronto, Ontario, Canada.


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Dr Dawson and colleagues conducted this phase 3 trial (NRT/RTOG 1112; ClinicalTrials.gov Identifier: NCT01730937) in 177 patients with locally advanced HCC. The patients were unsuitable for, refractory to, or had disease recurrence after resection, radiofrequency ablation, or transarterial chemoembolization.

At baseline, the median age was 66 years (range, 27-84), and 85% of patients were men. Forty-one percent of patients had hepatitis C, 74% had macrovascular invasion, and 82% had BCLC stage C disease.

Patients were randomly assigned to undergo SBRT followed by sorafenib (n=85) or to receive sorafenib alone (n=92). 

The trial was closed to accrual early due to the change in standard-of-care systemic therapy for HCC.

The study’s primary endpoint was OS, and SBRT improved OS. The median OS was 15.8 months in the SBRT arm and 12.3 months in the sorafenib-alone arm (hazard ratio [HR], 0.77; 90% CI, 0.59-1.01; P =.055). The 12-month OS rate was 53% with sorafenib alone and 59% with SBRT plus sorafenib. The 24-month OS rate was 23% and 33%, respectively.

The significant OS benefit with SBRT persisted in a multivariable analysis adjusted by performance status, M stage, Child Pugh score, and macrovascular involvement (HR, 0.72; 95% CI, 0.52-0.99; P =.042).

Dr Dawson pointed out that patients with more advanced HCC, including those with macrovascular invasion, tended to derive a greater benefit from the addition of SBRT to sorafenib.

Dr Dawson and colleagues also found that PFS was improved with SBRT. The median PFS was 9.2 months in the SBRT arm and 5.5 months with sorafenib alone (HR, 0.55; 95% CI, 0.40-0.75; P =.0001). 

TTP was improved with SBRT as well. The median TTP was 18.5 months in the SBRT arm and 9.5 months in the sorafenib-alone arm (HR, 0.69; 95% CI, 0.48-0.99; P =.034). 

The rate of grade 3 or higher treatment-related adverse events (TRAEs) was 42% with sorafenib alone and 47% with SBRT plus sorafenib. The most common grade 3 or higher TRAEs in the SBRT arm were aspartate transaminase elevation (n=5) and platelet level decrease (n=6).

There were 2 fatal TRAEs in the sorafenib-alone arm (hepatic failure and death not otherwise specified) and 1 in the SBRT arm (lung infection). 

“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,” Dr Dawson concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Dawson LA, Winter K, Knox J, et al. NRG/RTOG 1112: Randomized phase III study of sorafenib vs. stereotactic body radiation therapy (SBRT) followed by sorafenib in hepatocellular carcinoma (HCC) (NCT01730937). ASTRO 2022. October 23-26, 2022. Abstract LBA 01.