FDA Approval Summary: Ramucirumab for Gastric Cancer
Cet article passe en revue les données ayant servi de base à l'autorisation de mise sur le marché délivrée en 2014 par la FDA pour le ramucirumab dans le traitement des patients atteints d'un adénocarcinome gastrique de stade avancé ou métastatique
The FDA approved ramucirumab (CYRAMZA®, Eli Lilly and Company) for previously-treated patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma initially as monotherapy (April 21, 2014) and subsequently as combination therapy with paclitaxel (November 5, 2014). In the monotherapy trial, 355 patients in the indicated population were randomly allocated (2:1) to receive ramucirumab or placebo 8 mg/kg intravenously every 2 weeks. In the combination trial, 665 patients were randomly allocated (1:1) to receive ramucirumab or placebo 8 mg/kg intravenously every 2 weeks in combination with paclitaxel 80 mg/m2 on Days 1, 8 and 15 of 28-day cycles. Overall survival (OS) was increased in patients who received ramucirumab in both the monotherapy (HR 0.78; 95% CI, 0.60-0.998, log rank p=0.047) and combination trials (HR 0.81; 95% CI, 0.68-0.96; p=0.017). The most common adverse reactions were hypertension and diarrhea in the monotherapy trial and fatigue, neutropenia, diarrhea, and epistaxis in the combination trial. Because of concerns about the robustness of the monotherapy trial results, FDA approved the original application after receiving the results of the combination trial confirming the OS effect. Based on exploratory exposure-response analyses, there is residual uncertainty regarding the optimal dose of ramucirumab.
Clinical Cancer Research , résumé, 2015