title: International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1.
abstract: OBJECTIVE
  We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) combined with carboplatin/paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non-small-cell lung cancer (NSCLC) and in the subset of patients with adenocarcinoma.
  
  
  METHODS
  Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m(2)) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS.
  
  
  RESULTS
  A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment.
  
  
  CONCLUSIONS
  Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.
authors: University of Turin, S. Luigi Hospital, Turin, Italy. scagliotti@ihnet.it
authors: Giorgio V
authors: GV
authors: Scagliotti
authors: Ihor
authors: I
authors: Vynnychenko
authors: Keunchil
authors: K
authors: Park
authors: Yukito
authors: Y
authors: Ichinose
authors: Kaoru
authors: K
authors: Kubota
authors: Fiona
authors: F
authors: Blackhall
authors: Robert
authors: R
authors: Pirker
authors: Rinat
authors: R
authors: Galiulin
authors: Tudor-Eliade
authors: TE
authors: Ciuleanu
authors: Oleksandr
authors: O
authors: Sydorenko
authors: Mircea
authors: M
authors: Dediu
authors: Zsolt
authors: Z
authors: Papai-Szekely
authors: Natividad Martinez
authors: NM
authors: Banaclocha
authors: Sheryl
authors: S
authors: McCoy
authors: Bin
authors: B
authors: Yao
authors: Yong-Jiang
authors: YJ
authors: Hei
authors: Francesco
authors: F
authors: Galimi
authors: David R
authors: DR
authors: Spigel
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009841:Oligonucleotides; D017239:Paclitaxel / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; D016190:Carboplatin; D040262:Receptors, Vascular Endothelial Growth Factor; C519562:imetelstat; D017239:Paclitaxel