title: A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer.
abstract: BACKGROUND
  Targeted agents presently available for mutant KRAS metastatic colorectal cancer (mCRC) are bevacizumab and aflibercept. We evaluated the efficacy and safety of conatumumab (an agonistic monoclonal antibody against human death receptor 5) and ganitumab (a monoclonal antibody against the type 1 insulin-like growth factor receptor) combined with standard FOLFIRI chemotherapy as a second-line treatment in patients with mutant KRAS mCRC.
  
  
  METHODS
  Patients with mutant KRAS metastatic adenocarcinoma of the colon or rectum refractory to fluoropyrimidine- and oxaliplatin-based chemotherapy were randomized 1 : 1 : 1 to receive intravenous FOLFIRI plus conatumumab 10 mg/kg (Arm A), ganitumab 12 mg/kg (Arm B), or placebo (Arm C) Q2W. The primary end point was progression-free survival (PFS).
  
  
  RESULTS
  In total, 155 patients were randomized. Median PFS in Arms A, B, and C was 6.5 months (HR, 0.69; P = 0.147), 4.5 months (HR, 1.01; P = 0.998), and 4.6 months, respectively; median overall survival was 12.3 months (HR, 0.89; P = 0.650), 12.4 months (HR, 1.27; P = 0.357), and 12.0 months; and objective response rate was 14%, 8%, and 2%. The most common grade ≥3 adverse events in Arms A/B/C included neutropenia (30%/25%/18%) and diarrhea (18%/2%/10%).
  
  
  CONCLUSIONS
  Conatumumab, but not ganitumab, plus FOLFIRI was associated with a trend toward improved PFS. Both combinations had acceptable toxicity.
authors.affiliation: Rocky Mountain Cancer Center, Denver, USA. Electronic address: allen.cohn@usoncology.com.
authors.forename: A L
authors.initials: AL
authors.lastname: Cohn
authors.affiliation: Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona.
authors.forename: J
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Medical Oncology Department, Hospital Clinic de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Maurel
authors.affiliation: Maria Skodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Nowara
authors.affiliation: Hospital Clinico San Carlos, Servicio de Oncologíca Medíca, Madrid, and Instituto Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sastre
authors.affiliation: Department of Internal Medicine, National University Hospital, Singapore, Singapore.
authors.forename: B Y S
authors.initials: BYS
authors.lastname: Chuah
authors.affiliation: Samara Regional Oncology Dispensary, Samara.
authors.forename: M V
authors.initials: MV
authors.lastname: Kopp
authors.affiliation: Clinical Oncology Dispensary of the Republic of Bashkortostan, Ufa, Russia.
authors.forename: D D
authors.initials: DD
authors.lastname: Sakaeva
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia.
authors.forename: E P
authors.initials: EP
authors.lastname: Mitchell
authors.affiliation: Amgen Inc., South San Francisco.
authors.forename: S
authors.initials: S
authors.lastname: Dubey
authors.affiliation: Amgen Inc., South San Francisco.
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Amgen Inc., Thousand Oaks.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Hei
authors.affiliation: Amgen Inc., Thousand Oaks.
authors.forename: F
authors.initials: F
authors.lastname: Galimi
authors.affiliation: Amgen Inc., Thousand Oaks.
authors.forename: I
authors.initials: I
authors.lastname: McCaffery
authors.affiliation: Amgen Inc., Seattle, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Amgen Inc., Thousand Oaks.
authors.forename: R
authors.initials: R
authors.lastname: Loberg
authors.affiliation: Amgen Inc., Seattle, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cottrell
authors.affiliation: Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: S-P
authors.initials: SP
authors.lastname: Choo
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D017452:Receptors, IgG / Q000235:genetics; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C496124:FCGR3A protein, human; D018969:Insulin-Like Growth Factor Binding Proteins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; C554537:conatumumab; D000077146:Irinotecan; C545764:ganitumab; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: FOLFIRI; KRAS; conatumumab; ganitumab; metastatic colorectal cancer