Addition of SBRT to Sorafenib for Patients With Locally Advanced Hepatocellular Carcinoma

Laura Dawson, MD, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, discusses the results of the phase 3 NRG Oncology/RTOG 1112 study comparing stereotactic body radiotherapy (SBRT) followed by sorafenib to sorafenib alone for patients with locally advanced hepatocellular carcinoma.

Dr Dawson concluded, “This study emphasizes the importance of radiotherapy in treating hepatocellular carcinoma patients…[and] provides very strong rationale for adding radiotherapy into future randomized trials’ questions.”

Transcript:

Hi, my name is Laura Dawson. I'm professor and chair of the Department of Radiation Oncology at the University of Toronto, and I'm a practicing radiation oncologist at the Radiation Medicine program at Princess Margaret UHN in Toronto. It's my pleasure to talk to you briefly about the results of the NRG/RTOG 1112 randomized study.

That was a study of SBRT and sorafenib compared to sorafenib alone for patients with advanced hepatocellular carcinoma. This study randomized 193 patients, 177 who were eligible, and it was stopped earlier than anticipated as the standard of care systemic therapy had changed to immunotherapy. Nonetheless, the statistical analysis and hypothesis remained the same with the hypothesis that the addition of radiotherapy would improve overall survival with a hazard ratio 0.72. These patients had advanced cancer. The median tumor diameter was 7.8 cm with up to 20 cm tumors permitted, and any degree of macrovascular invasion was permitted. In fact, 74% of patients had invasion of the cancer into their hepatic vein/portal vein, including 64% who had invasion into the main right or left portal vein or main portal vein. All patients were suitable for tyrosine kinase inhibitor therapy and thus they had good liver function, Child-Pugh A liver function.

Most patients received the treatment as planned. There was 21% of patients who on the sorafenib alone arm crossed over to receive SBRT, and the median dose of radiation delivered was 35 [Gray] in 5 fractions and up to 50 Gray in 5 fractions, with the lowest dose of 27.5 in 5 fractions. There was personalization of the dose needed because many of these cancers were advanced adjacent to dose-limiting normal tissues, and in order to spear enough liver so that there was not a high toxicity risk.

The bottom line is this study did show improved survival. The median overall survival was improved from 12.3 months to 15.5 months. And when a priori prognostic factors were considered —presence of metastasis performance status, degree of macrovascular invasion, as well as liver function were considered— the improvement in overall survival had a hazard ratio of 0.72 and a P value 0.042. Similarly, the addition of radiotherapy improved progression-free survival in a clinically important manner with statistical significance with a hazard ratio of 0.5, a P value of 0.001. The median progression-free survival improved from 5.5 months to 9.2 months with the addition of SBRT.

Furthermore, this treatment appeared well tolerated. In fact, there were similar grade 3 or higher related adverse events in this study, approximately 45%. And when looking at related grade 5adverse events, there were 2 deaths in the sorafenib alone arm and 1 in the sorafenib and SBRT arm. This highlights the complexity of looking at adverse events in patients with locally advanced cancers. The cancer itself can cause adverse events and underlying liver disease may mimic treatment related toxicity. And the best way to avoid important adverse events is to control the cancer.

In a hypothesis-generating secondary analysis of patients who consented for patient-reported quality of life, there was a higher proportion of patients who had improved quality of life 6 months after therapy in the group who received SBRT in addition to sorafenib, with that being 35% compared to 10% of patients who had improved quality of life in the sorafenib alone arm.

In conclusion, this study emphasizes the importance of radiotherapy in treating hepatocellular carcinoma patients. It shows the radiation responsiveness, in that the median dose was relatively low, 35 Gray in 5 fractions despite the treatment of very locally advanced cancers. Although the standard of care has changed, this provides very strong rationale for adding radiotherapy into future randomized trials’ questions. And I would hypothesize that the benefits will even be larger when we look at trials that compare the addition of radiotherapy to immunotherapy that is most commonly used in the first line for patients with advanced cancer now, thanks.

Source:

Dawson LA, Winter KA, Knox JJ, et al. Stereotactic body radiotherapy vs sorafenib alone in hepatocellular carcinoma: The NRG Oncology/RTOG 1112 phase 3 randomized clinical trial. JAMA Oncol. 2025;11(2):136-144. Doi:10.1001/jamaoncol.2024.5403