title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of MetastaticKRASMutant Colorectal Adenocarcinoma.
abstract: The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastaticKRASmutant colorectal carcinoma.
  
  
  
  Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro.
  
  
  
  Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed.
  
  
  
  In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n= 84), FOLFIRI/simtuzumab 200 mg (n= 85), and FOLFIRI/placebo (n= 80). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI],pvalue versus placebo; 1.32 [0.92, 1.89];p= .10), 5.4 months (1.45 [1.01, 2.06];p= .04), and 5.8 months. Median OS was 11.4 months (1.23 [0.80, 1.91];p= .25), 10.5 months (1.50 [0.98, 2.30];p= .06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastaticKRASmutant CRC patients.
  
  
  
  The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastaticKRASmutant CRC.The Oncologist2017;22:243-e8.
authors.affiliation: David Geffen School of Medicine at the University of California, Los Angeles, California, USA jrhecht@mednet.ucla.edu.
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
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: Yingsi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Bendell
authors.affiliation: The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Udit
authors.initials: U
authors.lastname: Verma
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; C000613471:simtuzumab; D016283:Proto-Oncogene Proteins p21(ras); D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin