FDA Approval Summary: Ramucirumab for Gastric Cancer.

Abstract

The FDA approved ramucirumab (CYRAMZA; Eli Lilly and Company) for previously treated patients with advanced or metastatic gastric or gastroesophageal junction 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/m(2) 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% confidence interval (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.

• Authors: Sandra J Casak, Ibilola Fashoyin-Aje, Steven J Lemery, Lillian Zhang, Runyan Jin, Hongshan Li, Liang Zhao, Hong Zhao, Hui Zhang, Huanyu Chen, Kun He, Michele Dougherty, Rachel Novak, Sarah Kennett, Sachia Khasar, Whitney Helms, Patricia Keegan, Richard Pazdur
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 21 Issue 15 Pg. 3372-6 (Aug 01 2015) ISSN: 1557-3265 [Electronic] United States
• PMID: 26048277 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• ramucirumab
• Paclitaxel

Topics

• Adenocarcinoma (drug therapy, pathology)
• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Disease-Free Survival
• Drug Approval
• Drug-Related Side Effects and Adverse Reactions (pathology)
• Esophageal Neoplasms (drug therapy, pathology)
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Paclitaxel (administration & dosage, adverse effects)
• Stomach Neoplasms (drug therapy, pathology)