Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1)
Mené entre 2017 et 2020 sur 262 patients atteints d'un carcinome hépatocellulaire de stade avancé et n'ayant pas reçu de traitement systémique, cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie globale, d'un traitement comportant une chimiothérapie interventionnelle par perfusion artérielle hépatique de fluorouracile, de leucovorine et d'oxaliplatine par rapport à une monothérapie systémique par sorafénib
PURPOSE: Interventional hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) displayed an encouraging safety profile and antitumor activity in a previous phase II trial and a propensity-score-matching study involving patients with locally advanced hepatocellular carcinoma (HCC). METHODS: In this open-label, phase III trial, patients with advanced HCC, previously untreated with systemic therapy, were randomly assigned in a 1:1 ratio to receive HAIC-FO or sorafenib. The primary end point was overall survival (OS) in the intention-to-treat population. An exploratory model for predicting the efficacy of HAIC-FO on the basis of genomic sequencing was developed. RESULTS: Between May 2017 and May 2020, 262 patients were randomly assigned. The median tumor size was 11.2 cm (interquartile range, 8.5-13.7 cm). Macrovascular invasion was present in 65.6%, and the percentage of patients with > 50% tumor volume involvement of the liver and/or Vp-4 portal vein tumor thrombosis was 49.2%. At data cutoff (October 31, 2020), median OS was 13.9 months for HAIC-FO and 8.2 for sorafenib (hazard ratio [HR] 0.408; 95% CI, 0.301 to 0.552; P < .001). Tumor downstaging occurred in 16 (12.3% of 130) patients receiving HAIC-FO, including 15 receiving curative surgery or ablation, and finally achieving a median OS of 20.8 months, with a 1-year OS rate of 93.8%. In high-risk subpopulations, OS was significantly longer with HAIC-FO than with sorafenib (10.8 months v 5.7 months; HR 0.343; 95% CI, 0.219 to 0.538; P < .001). A newly developed 15-mutant-gene prediction model identified 83% of patients with response to HAIC-FO. HAIC-FO responders had longer OS than HAIC-FO nonresponders (19.3 months v 10.6 months; HR 0.323; 95% CI, 0.186 to 0.560; P = .002). CONCLUSION: HAIC-FO achieved better survival outcomes than sorafenib in advanced HCC, even in association with a high intrahepatic disease burden.