title: Safety of Onartuzumab in Patients with Solid Tumors: Experience to Date from the Onartuzumab Clinical Trial Program.
abstract: BACKGROUND
  Onartuzumab, a recombinant humanized monovalent monoclonal antibody directed against MET, the receptor for the hepatocyte growth factor, has been investigated for the treatment of solid tumors. This publication describes the safety profile of onartuzumab in patients with solid tumors using data from the global onartuzumab clinical development program.
  
  
  METHODS
  Adverse event (AE) and laboratory data from onartuzumab phase II/III studies were analyzed and coded into standardized terms according to industry standards. The severity of AEs was assessed using the NCI Common Toxicity Criteria, Version 4. Medical Dictionary for Regulatory Activities (MedDRA) AEs were grouped using the standardized MedDRA queries (SMQs) "gastrointestinal (GI) perforation", "embolic and thrombotic events, venous (VTE)", and "embolic and thrombotic events, arterial (ATE)", and the Adverse Event Group Term (AEGT) "edema." The safety evaluable populations (patients who received at least one dose of study treatment) for each study were included in this analysis.
  
  
  RESULTS
  A total of 773 onartuzumab-treated patients from seven studies (phase II, n = 6; phase III, n = 1) were included. Edema and VTEs were reported in onartuzumab-treated patients in all seven studies. Edema events in onartuzumab arms were generally grade 1-2 in severity, observed more frequently than in control arms and at incidences ranging from 25.4-65.7% for all grades and from 1.2-14.1% for grade 3. Hypoalbuminemia was also more frequent in onartuzumab arms and observed at frequencies between 77.8% and 98.3%. The highest frequencies of all grade and grade ≥3 VTE events were 30.3% and 17.2%, respectively in onartuzumab arms. The cumulative incidence of all grade ATE events ranged from 0-5.6% (grade ≥3, 0-5.1%) in onartuzumab arms. The frequency of GI perforation was below 10% in all studies; the highest estimates were observed in studies with onartuzumab plus bevacizumab for all grades (0-6.2%) and grade ≥3 (0-6.2%).
  
  
  CONCLUSIONS
  The frequencies of VTE, ATE, GI perforation, hypoalbuminemia, and edema in clinical studies were higher in patients receiving onartuzumab than in control arms; these are considered to be expected events in patients receiving onartuzumab.
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Roland
authors.initials: R
authors.lastname: Morley
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Alison
authors.initials: A
authors.lastname: Cardenas
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Hawkins
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Virginia
authors.initials: V
authors.lastname: Paton
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: See-Chun
authors.initials: SC
authors.lastname: Phan
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Merchant
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Jessie
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Koralek
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Luhn
authors.affiliation: Genentech Inc, South San Francisco, CA, United States of America.
authors.forename: Wassim
authors.initials: W
authors.lastname: Aldairy
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D004487:Edema / Q000209:etiology*; D006801:Humans; D034141:Hypoalbuminemia / Q000209:etiology*; D007416:Intestinal Perforation / Q000209:etiology*; D009369:Neoplasms / Q000188:drug therapy; D013923:Thromboembolism / Q000209:etiology*; D054556:Venous Thromboembolism / Q000209:etiology*
chemical_list: D000911:Antibodies, Monoclonal; C584058:onartuzumab