title: A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma.
abstract: The safety profile in the gemcitabine/simtuzumab group was similar to that in the gemcitabine/placebo group.The addition of simtuzumab to gemcitabine does not improve clinical outcomes in patients with metastatic pancreatic adenocarcinoma ABSTRACT: Background.The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors.
  
  
  
  Adult patients with metastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m2, in combination with 200 or 700 mg simtuzumab or placebo. Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR), and safety.
  
  
  
  Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median follow-up of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI],pvalue vs placebo: 1.09 [0.74-1.61];p= .73), 3.5 months (1.13 [0.76-1.66],p= .61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 [0.57-1.22];p= .28), 5.9 months (1.07 [0.73-1.55];p= .69), and 5.7 months, respectively. ORRs were 13.9%, 14.5%, and 23.5%, respectively. Simtuzumab was well tolerated.
  
  
  
  The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.The Oncologist2017;22:241-e7.
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA a-benson@northwestern.edu.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Wainberg
authors.affiliation: David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.affiliation: Budgetary Healthcare Institution of Omsk Region, Clinical Oncologic Dispensary, Omsk, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Vyushkov
authors.affiliation: Gilead Sciences, Inc., Foster City, California, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Dong
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Bendell
authors.affiliation: South Carolina Oncology Associates, Columbia, South Carolina, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Kudrik
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010919:Placebos; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D010919:Placebos; D003841:Deoxycytidine; C000613471:simtuzumab; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human; D000093542:Gemcitabine