title: 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.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, U.S. Food and Drug Administration, Silver Spring, Maryland. Sandra.Casak@fda.hhs.gov.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Casak
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Ibilola
authors.initials: I
authors.lastname: Fashoyin-Aje
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lemery
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Lillian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Runyan
authors.initials: R
authors.lastname: Jin
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Li
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Office of Biostatistics, Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Office of Biostatistics, Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Office of Biostatistics, Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Michele
authors.initials: M
authors.lastname: Dougherty
authors.affiliation: Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Novak
authors.affiliation: Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kennett
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Sachia
authors.initials: S
authors.lastname: Khasar
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Whitney
authors.initials: W
authors.lastname: Helms
authors.affiliation: Office of Hematology and Oncology Products, Office of New Drugs, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Office of Biostatistics, Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018572:Disease-Free Survival; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017239:Paclitaxel; D000096662:Ramucirumab