title: Personalized medicine for patients with advanced cancer in the phase I program at MD Anderson: validation and landmark analyses.
abstract: OBJECTIVE
  The purpose of this study was to confirm our previous results that targeted agents matched with tumor molecular alterations were associated with improved outcomes compared with nonmatched therapy in patients with advanced cancer.
  
  
  METHODS
  Outcomes of patients who were referred for treatment on phase I clinical trials at The University of Texas MD Anderson Cancer Center (Houston, TX) from March 2011 to January 2012 were compared between those who had received targeted therapy and those for whom no targeted therapy was available. Two-month landmark analyses for overall and progression-free survival (PFS) combining previously published and validation cohort patient data were performed.
  
  
  RESULTS
  In patients with one alteration, matched therapy (n = 143) compared with treatment without matching (n = 236) was associated with a higher objective response rate (12% vs. 5%; P < 0.0001), longer PFS (median, 3.9 vs. 2.2 months; P = 0.001), and longer survival (median, 11.4 vs. 8.6 months; P = 0.04). In multivariate analysis, matched therapy was an independent factor predicting response (P < 0.015) and PFS (P < 0.004). Two-month landmark analyses in the matched therapy group demonstrated that the median survival of responders was 30.5 months compared with 11.3 months for nonresponders (P = 0.01); and the median PFS was 38.7 months compared with 5.9 months, respectively (P < 0.0001). The respective values in the nonmatched therapy group were 9.8 and 9.4 months (P = 0.46) and 8.5 and 4.2 months (P = 0.18).
  
  
  CONCLUSIONS
  This validation analysis confirms our previous observations. In the matched therapy group, 2-month landmark analyses demonstrated that responders have longer survival and PFS than nonresponders.
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas. atsimber@mdanderson.org.
authors.forename: Apostolia-Maria
authors.initials: AM
authors.lastname: Tsimberidou
authors.affiliation: Department of Biostatistics, West Virginia University Health Science Center, Morgantown, West Virginia.
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape
authors.affiliation: Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Internal Medicine, Moores Cancer Center-University of California San Diego, LaJolla, California.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Donald
authors.initials: D
authors.lastname: Berry
mesh_terms: D000328:Adult; D000368:Aged; D017321:Clinical Trials, Phase I as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000401:mortality*; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D057285:Precision Medicine / Q000379:methods / Q000401:mortality*; D016896:Treatment Outcome