title: Impact of molecular profiling on overall survival of patients with advanced ovarian cancer.
abstract: OBJECTIVE
  Patients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC.
  
  
  RESULTS
  Patients in the Matched cohort had a median OS of 36 months compared to 27 months for patients in the Unmatched cohort (HR 0.62, 95% CI 0.41-0.96; p < 0.03). Individual biomarkers were analyzed, with TUBB3, and PGP prognostic for survival. Biomarker analysis also identified a molecular subtype (positive for at least two of the following markers: ERCC1, RRM1, TUBB3, PGP) with particularly poor overall survival.
  
  
  METHODS
  224 patients from a commercial registry (NCT02678754) with stage IIIC/IV EOC at diagnosis, or restaged to IIIC/IV EOC at the time of molecular profiling, were retrospectively divided into two cohorts based on whether or not the drugs they received matched their profile recommendations. The Matched cohort received no drugs predicted to be lack-of-benefit while the Unmatched cohort received at least one drug predicted to be lack-of-benefit. Profile biomarker/drug associations were based on multiple test platforms including immunohistochemistry, fluorescent in situ hybridization and DNA sequencing.
  
  
  CONCLUSIONS
  This report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit.
authors.affiliation: University of Cincinnati Cancer Institute, Cincinnati, OH, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Spetzler
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Xiao
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Burnett
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Maney
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Voss
authors.affiliation: Caris Life Sciences, Phoenix, AZ, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Reddy
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Burger
authors.affiliation: Western Pennsylvania Gynecological Oncology, Mars, PA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krivak
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Powell
authors.affiliation: Prince of Wales Hospital, Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Friedlander
authors.affiliation: VCU Massey Cancer Center, Richmond, VA, USA.
authors.forename: William
authors.initials: W
authors.lastname: McGuire
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: cancer; molecular; ovarian; profiling; survival