title: Motesanib plus carboplatin/paclitaxel in patients with advanced squamous non-small-cell lung cancer: results from the randomized controlled MONET1 study.
abstract: BACKGROUND
  The phase 3 MONET1 study evaluated motesanib (a small-molecule inhibitor of vascular endothelial growth factor receptors) plus carboplatin/paclitaxel versus placebo plus carboplatin/paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC). Treatment and enrollment of patients with squamous histology were permanently discontinued following higher early mortality and gross hemoptysis in those with squamous NSCLC who received motesanib. Enrollment of patients with nonsquamous histology was temporarily halted, but resumed following a protocol amendment (Scagliotti et al. J Clin Oncol. 2012;30:2829-2836). Herein, we report data from the squamous cohort.
  
  
  METHODS
  Patients with stage IIIB/IV or recurrent squamous NSCLC (without prior systemic therapy for advanced disease) received up to six 3-week cycles of chemotherapy (carboplatin, area under the curve 6 mg/mL•min/paclitaxel, 200 mg/m) and were randomized 1:1 to receive motesanib 125 mg (Arm A) or placebo (Arm B) once daily. The primary end point was overall survival.
  
  
  RESULTS
  Three-hundred and sixty patients with squamous NSCLC were randomized (Arm A, n = 182; Arm B, n = 178) between July 2007 and November 2008. Twenty-three patients (13%) in Arm A and 10 (6%) in Arm B had fatal adverse events within the first 60 days of treatment. Among these, six patients in Arm A, but none in Arm B, had fatal bleeding events. At final analysis, serious adverse events had occurred in 47% of patients in Arm A and 29% of patients in Arm B. Median overall survival was similar in Arms A and B (11.1 versus 10.7 months).
  
  
  CONCLUSIONS
  Motesanib plus carboplatin/paclitaxel had unacceptable toxicity compared with carboplatin/paclitaxel alone in patients with advanced squamous NSCLC.
authors.affiliation: *Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy; †Thoracic Surgery Department, Zaporizhzhya State Medical University, Zaporizhzhya, Ukraine; ‡Sumy Regional Oncology Centre, Sumy State University, Sumy, Ukraine; §Centrul de Oncologie Medicala, Iasi, Romania; ‖Central Hospital Bad Berka, Bad Berka, Germany; ¶Department of Medical Oncology, The Christie National Health Services Foundation Trust, Manchester, United Kingdom; #Department of Biostatistics & Epidemiology, Amgen Inc., South San Francisco; **Department of Oncology, Amgen Inc., Thousand Oaks, CA; and ††Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Sydorenko
authors.forename: Ihor
authors.initials: I
authors.lastname: Vynnychenko
authors.forename: Constantin
authors.initials: C
authors.lastname: Volovat
authors.forename: Claus-Peter
authors.initials: CP
authors.lastname: Schneider
authors.forename: Fiona
authors.initials: F
authors.lastname: Blackhall
authors.forename: Sheryl
authors.initials: S
authors.lastname: McCoy
authors.forename: Yong-Jiang
authors.initials: YJ
authors.lastname: Hei
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D006469:Hemoptysis / Q000139:chemically induced*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D009841:Oligonucleotides; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate
chemical_list: D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; D016190:Carboplatin; C519562:imetelstat; D017239:Paclitaxel