SBRT plus sorafenib improves survival in hepatocellular carcinoma
Treatment with stereotactic body radiation therapy (SBRT) followed by sorafenib results in better overall (OS) and progression-free survival (PFS), with no increase in adverse events (AEs), compared with sorafenib monotherapy in patients with hepatocellular carcinoma (HCC), as shown in a phase III study presented at the 2023 ASCO GI Cancers Symposium.
This finding also suggests better quality of life (QOL) at 6 months, according to the researchers, led by Laura A. Dawson from the Princess Margaret Cancer Centre in Toronto, Canada.
Patients who had new or recurrent HCC, were unsuitable for surgery, ablation, or transarterial chemoembolization, with Zubrod performance status (PS) 0‒2, Child-Pugh (CP) A, Barcelona Clinic Liver Cancer (BCLC) stage B or C, ≤5 HCCs, sum of hepatic HCCs ≤20 cm, and distant metastases ≤3 cm were eligible for inclusion.
Dawson and her team randomized eligible patients 1:1 to sorafenib 400 mg BID or SBRT (27.5-50 Gy in five fractions) followed by sorafenib 200 mg BID, increased to 400 mg BID after 28 days. They estimated OS and PFS using Kaplan-Meier and compared the two arms using log-rank test. Finally, they analysed treatment effect using Cox proportional hazards models.
Of the 193 patients identified from April 2013 to March 2021 from 23 sites, 177 (median age 66 years) met the eligibility criteria and were randomized to sorafenib alone (n=92) or SBRT plus sorafenib (n=85). Of these, 41 percent had hepatitis C and 19 percent had hepatitis B or B/C. [ASCO GI 2023, abstract 489]
BCLC stage C was found in 82 percent of patients, and macrovascular invasion (MVI) was observed in 74 percent, while 63 percent had VP3 or VP4 MVI. Metastases occurred in 4 percent of participants. The max diameter of HCCs had a median sum of 8.2 cm for sorafenib and 6.7 cm for SBRT plus sorafenib. Of note, less than half of the patients (40 percent) had a single HCC.
Median follow-up was 13.2 months for all patients and 33.7 months for those who remained alive during the study period. Among patients who received sorafenib alone, 22 percent underwent SBRT after discontinuing sorafenib.
A total of 153 OS events were recorded, with median OS improving from 12.3 months (90 percent confidence interval [CI], 10.6‒14.3) with sorafenib alone to 15.8 months (90 percent CI, 11.4‒19.2) with SBRT plus sorafenib (hazard ratio [HR], 0.77; 1-sided p=0.0554).
Notably, OS significantly improved for SBRT plus sorafenib (HR, 0.72, 95 percent CI, 0.52‒0.99; 2-sided Cox p=0.042) after adjusting for PS, metastasis stage, CP A5 vs 6, and degree of MVI.
PFS also improved from a median of 5.5 months (95 percent CI, 3.4‒6.3) with sorafenib to 9.2 months (95 percent CI, 7.5‒11.9) with SBRT plus sorafenib (HR, 0.55, 95 percent CI, 0.40‒0.75; 2-sided p=0.0001).
In terms of AEs, eight patients had grade (G) 3+ bleeding: five in the sorafenib arm (one G3 variceal, two G3 upper gastrointestinal [GI], one G3 hepatic, and one G4 abdominal) and three post-SBRT plus sorafenib (two G3 upper GI and one G3 lower GI). Treatment-related G3+ AEs did not differ significantly between groups (sorafenib: 42 percent vs SBRT plus sorafenib: 47 percent; p=0.52), with three G5 AEs noted (sorafenib: one hepatic failure and one death; SBRT plus sorafenib: one lung infection).
Finally, 20 patients in the sorafenib arm and 17 in the SBRT arm consented to QOL assessments at baseline and 6 months. Of these, 10 percent and 35 percent, respectively, saw improvements in FACT-Hep score.