Safety and Preliminary Efficacy of Ramucirumab in Combination with FOLFOX4 in Patients with Advanced Hepatocellular Carcinoma: A Nonrandomized, Open-Label, Phase Ib Study
Mené sur 8 patients atteints d'un carcinome hépatocellulaire de stade avancé, cet essai non randomisé de phase IB évalue la dose maximale tolérée du ramucirumab en combinaison avec une chimiothérapie de type FOLFOX4 et analyse les caractéristiques pharmacocinétiques de cette combinaison
Background : The objective of this study was to investigate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of ramucirumab plus FOLFOX4 as first‐line treatment in patients with advanced hepatocellular carcinoma (HCC). Methods : Patients received ramucirumab (8 mg/kg) intravenously (IV) on day 1, followed by FOLFOX4 (oxaliplatin 85 mg/m2 IV on day 1, folinic acid 200 mg/m2 IV, bolus fluorouracil [5‐FU] 400 mg/m2, and a continuous infusion of 5‐FU 600 mg/m2 over 22 hours, on days 1 and 2) every 2 weeks. The primary endpoint was to assess the safety and tolerability of the combination therapy. Results : Eight patients (6 men, 2 women) were treated; all eight patients experienced at least one treatment‐emergent adverse event (TEAE) of grade ≥3. Dose‐limiting toxicities occurred in three patients (37.5%): hepatic hemorrhage (grade 4), blood bilirubin increased (grade 3), and febrile neutropenia (grade 3). Two patients discontinued study because of hepatic hemorrhage (grade 4) and blood bilirubin increase (grade 3). Six deaths occurred due to progressive disease, and no deaths due to TEAEs. Conclusion : There were no unexpected safety findings with ramucirumab plus FOLFOX4 based on the known safety and toxicity of this regimen. The combination was not sufficiently tolerated in patients with advanced HCC at the specified dose and schedule.
The Oncologist 2020