title: Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative.
abstract: OBJECTIVE
  We initiated a personalized medicine program in the context of early clinical trials, using targeted agents matched with tumor molecular aberrations. Herein, we report our observations.
  
  
  METHODS
  Patients with advanced cancer were treated in the Clinical Center for Targeted Therapy. Molecular analysis was conducted in the MD Anderson Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Patients whose tumors had an aberration were treated with matched targeted therapy, when available. Treatment assignment was not randomized. The clinical outcomes of patients with molecular aberrations treated with matched targeted therapy were compared with those of consecutive patients who were not treated with matched targeted therapy.
  
  
  RESULTS
  Of 1,144 patients analyzed, 460 (40.2%) had 1 or more aberration. In patients with 1 molecular aberration, matched therapy (n = 175) compared with treatment without matching (n = 116) was associated with a higher overall response rate (27% vs. 5%; P < 0.0001), longer time-to-treatment failure (TTF; median, 5.2 vs. 2.2 months; P < 0.0001), and longer survival (median, 13.4 vs. 9.0 months; P = 0.017). Matched targeted therapy was associated with longer TTF compared with their prior systemic therapy in patients with 1 mutation (5.2 vs. 3.1 months, respectively; P < 0.0001). In multivariate analysis in patients with 1 molecular aberration, matched therapy was an independent factor predicting response (P = 0.001) and TTF (P = 0.0001).
  
  
  CONCLUSIONS
  Keeping in mind that the study was not randomized and patients had diverse tumor types and a median of 5 prior therapies, our results suggest that identifying specific molecular abnormalities and choosing therapy based on these abnormalities is relevant in phase I clinical trials.
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. atsimber@mdanderson.org
authors.forename: Apostolia-Maria
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Iskander
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Donald
authors.initials: D
authors.lastname: Berry
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002173:Cancer Care Facilities; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D052138:Genes, Neoplasm; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D057285:Precision Medicine; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents