Results From the Phase 3 NRG/RTOG 1112 Study of Sorafenib in HCC

Laura A. Dawson, MD, FRCPC, Princess Margaret Cancer Centre, Toronto, Ontario, discusses findings from the NRG/RTOG 1112 study (NCT01730937) of stereotactic body radiation therapy (SBRT) followed by sorafenib (Nexavar) vs sorafenib alone in hepatocellular carcinoma (HCC).

The randomized phase 3 NRG/RTOG 1112 study aimed to determine whether SBRT followed by sorafenib improves overall survival (OS), progression-free survival (PFS) and quality of life compared with sorafenib alone in patients with HCC.

According to Dawson, 177 eligible patients were randomized in the study, including 92 to receive sorafenib alone and 85 to receive SBRT plus sorafenib. The median OS was 12.3 months (90% CI, 10.6-14.3) with sorafenib alone vs 15.8 months (90% CI, 11.4-19.2) with SBRT plus sorafenib (HR 0.77; P = .0554), and the median PFS was 5.5 months (95% CI, 3.4-6.3) vs 9.2 months (95% CI, 7.5-11.9).

For safety, treatment-related grade 3 or greater adverse events occurred in 42% of patients given the combination of SBRT and sorafenib vs 47% with sorafenib alone (P = 0.52). However, these were not of concern within the SBRT arm.

Transcription:

0:08 | One hundred and ninety-three patients were randomized. Of those patients, 177 met all of the eligibility criteria, and those are the patients that were the focus of the report. They were similar in terms of prognostic factors. Of note, approximately 3 quarters of the patients had microvascular invasion, and the great majority of those, close to 64%, had invasion into the main portal vein or the main right or left portal vein. So very large vessels, higher than what has been seen in other randomized studies of patients with liver cancer.

0:45 | The bottom line was that overall survival was improved from a median survival of 12.3 months with sorafenib to 15.8 months with SBRT and sorafenib. On a pre-planned multivariable analysis, the hazard ratio was 0.72, and the P value was .042. Similarly, there were improvements in progression-free survival and time-to-progression, a near doubling in both arms with good hazard ratios and statistical significance confirming the benefit.

1:20 | Interestingly, the adverse events were not of concern with the SBRT arm. In fact, grade 3 or higher events were similar in both arms, probably due to the cancer as the cancer was very advanced and can cause [adverse events] related to liver failure itself, so it's seen in about 3 quarters of patients. The grade 4 or 5 events were similar in both arms. There was a slight increase in GI adverse events with increasing enzymes and decreasing platelets that were grade 3 and reversible in patients who received SBRT.