title: Designs of preoperative biomarkers trials in oncology: a systematic review of the literature.
abstract: BACKGROUND
  The identification of predictive and pharmacodynamics (PD) biomarkers of efficacy of anticancer-targeted therapies is not always straightforward. To address this problem, preoperative trials have been set up. The present study aimed at evaluating how these trials are designed.
  
  
  METHODS
  We retrieved all preoperative oncology trials, defined as preoperative trials having a PD end point.
  
  
  RESULTS
  Only 56 trials met our selection criteria. Of these, 27 trials (48%) were randomized. Forty-nine trials (88%) evaluated at least a noncytotoxic agent. In 37 trials (66%), a single agent was administered. The most prevalent tumor type was breast cancer (59%). Median duration of accrual was 28 months (range: 9-98). In these trials, there was a mean of two patients included per month (range: 0-7). The date of surgery was fixed before study entry in 35 trials (62%), while surgery was set up after preoperative therapy in the remaining 21 trials (38%). In the former trials, median duration of preoperative therapy was 17 days (range: 1-112), whereas in the latter trials it ranged from 4 to 29 weeks. The primary end point was a PD end point in 26 of the 45 trials (58%) in which it was mentioned. One percent of patients could not undergo surgery as per protocol due to an adverse event. Statistically significant predictive and PD biomarkers were identified in 17 (30%) and 27 trials (48%), respectively.
  
  
  CONCLUSIONS
  Preoperative biomarkers trials are infrequent but safe and feasible. These trials often permit the identification of predictive and PD biomarkers.
authors.affiliation: Department of Biostatistics.
authors.forename: M
authors.initials: M
authors.lastname: Marous
authors.affiliation: Pharmacogenomics Unit.
authors.forename: I
authors.initials: I
authors.lastname: Bièche
authors.affiliation: Department of Biostatistics INSERM U900, Institut Curie, Paris.
authors.forename: X
authors.initials: X
authors.lastname: Paoletti
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France.
authors.forename: M
authors.initials: M
authors.lastname: Alt
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Canada.
authors.forename: A R A
authors.initials: AR
authors.lastname: Razak
authors.affiliation: Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Stathis
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France.
authors.forename: M
authors.initials: M
authors.lastname: Kamal
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, France EA7285, Versailles-Saint-Quentin-en-Yvelines University, Versailles, France Christophe.LeTourneau@curie.fr.
authors.forename: C
authors.initials: C
authors.lastname: Le Tourneau
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000601:surgery; D011300:Preoperative Care / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarker; oncology; pharmacodynamic; predictive; preoperative; trials