Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial
Mené sur 177 patients atteints d'un carcinome hépatocellulaire localement avancé (âge médian : 66 ans ; 84,7 % d'hommes), cet essai randomisé multicentrique de phase III évalue l'efficacité, du point de vue de la survie globale, de l'ajout d'une radiothérapie stéréotaxique avant un traitement par sorafénib
Résumé en anglais
Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, and data were analyzed from July 2022 to August 2023.Personalized SBRT, 27.5 to 50 Gy in 5 fractions.The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), adverse events, and quality of life.Of 193 patients randomized, 177 were eligible. Accrual was stopped early due to a change in standard-of-care systemic therapy. Of 177 included patients, 150 (84.7%) were male, and the median (IQR) age was 66 (60-72) years. Macrovascular invasion was seen in 131 (74.0%). As of July 1, 2022, the median OS was 12.3 months (90% CI, 10.6-14.3) with sorafenib vs 15.8 months (90% CI, 11.4-19.2) following SBRT and sorafenib (hazard ratio [HR], 0.77; 90% CI, 0.59-1.01; 1-sided P = .06). Adjusting for stratification factors, OS was improved with SBRT (HR, 0.72; 95% CI, 0.52-0.99; 2-sided P = .04). Median PFS was improved from 5.5 months (95% CI, 3.4-6.3) with sorafenib to 9.2 months (95% CI, 7.5-11.9) with SBRT and sorafenib (HR, 0.55; 95% CI, 0.40-0.75; 2-sided P < .001). Treatment-related grade 3 or higher adverse events were seen in 37 of 88 (42%) and 39 of 83 (47%) of patients treated with sorafenib vs SBRT and sorafenib, respectively (P = .52). There were 2 treatment-related deaths in the sorafenib group (death not otherwise specified and liver failure) and 1 in the SBRT and sorafenib group (lung infection). At 6 months, improved quality of life was seen in 2 of 20 (10%) and 6 of 17 (35%) of patients treated with sorafenib and SBRT and sorafenib, respectively.In this phase 3 randomized clinical trial, among patients with locally advanced HCC, SBRT was associated with a clinically important but not statistically significant improved overall survival compared with sorafenib alone.ClinicalTrials.gov Identifier: NCT01730937
