title: Feasibility of preemptive biomarker profiling for personalised early clinical drug development at a Comprehensive Cancer Center.
abstract: OBJECTIVE
  Multiple investigational drugs are currently explored in cancer patient populations defined by specific biomarkers. This demands a new process of patient selection for clinical trials.
  
  
  METHODS
  Starting January 1, 2012, preemptive biomarker profiling was offered at the West German Cancer Center to all patients with advanced non-small-cell lung (NSCLC) or colorectal cancer (CRC), who met generic study inclusion criteria. Tumour specimens were subjected to prespecified profiling algorithms to detect 'actionable biomarkers' by amplicon sequencing, in situ hybridisation and immunohistochemistry. The clinical course was closely monitored to offer trial participation whenever applicable.
  
  
  RESULTS
  Within 12 months, 267 patients (188 NSCLC, 79 CRC) were profiled. Estimated additional cost for biomarker profiling was 219615.51 EUR excluding histopathology workup and administration. The most prevalent biomarkers in pulmonary adenocarcinoma were KRAS mutations (29%), loss of PTEN expression (18%), EGFR mutations (9%), HER2 amplification (5%) and BRAF mutations (3%), while the prevalence of ALK translocations and PIK3CA mutations was extremely low. In pulmonary squamous cell carcinoma FGFR1 amplifications were found in 15%, PTEN expression was lost in 20% and DDR2 was mutated in a single case. KRAS mutations (41%) predominated in CRC, followed by loss of PTEN expression (16%), PIK3CA (5%) and BRAF (5%) mutations. So far 13 patients (5%) have entered biomarker-stratified clinical trials. Therapeutic decisions for approved drugs were guided in another 45 patients (17%).
  
  
  CONCLUSIONS
  Preemptive biomarker profiling can be implemented into the diagnostic algorithm of a large Comprehensive Cancer Center. Substantial investments in diagnostics and administration are required.
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Wiesweg
authors.forename: Saskia
authors.initials: S
authors.lastname: Ting
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.forename: Karl
authors.initials: K
authors.lastname: Worm
authors.forename: Stefan
authors.initials: S
authors.lastname: Kasper
authors.forename: Mitra
authors.initials: M
authors.lastname: Tewes
authors.forename: Anja
authors.initials: A
authors.lastname: Welt
authors.forename: Heike
authors.initials: H
authors.lastname: Richly
authors.forename: Johannes
authors.initials: J
authors.lastname: Meiler
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.forename: Jörg
authors.initials: J
authors.lastname: Hense
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Gauler
authors.forename: Jens
authors.initials: J
authors.lastname: Köhler
authors.forename: Wilfried E
authors.initials: WE
authors.lastname: Eberhardt
authors.forename: Kaid
authors.initials: K
authors.lastname: Darwiche
authors.forename: Lutz
authors.initials: L
authors.lastname: Freitag
authors.forename: Georgios
authors.initials: G
authors.lastname: Stamatis
authors.forename: Frank
authors.initials: F
authors.lastname: Breitenbücher
authors.forename: Jeremias
authors.initials: J
authors.lastname: Wohlschlaeger
authors.forename: Dirk
authors.initials: D
authors.lastname: Theegarten
authors.forename: Cordula
authors.initials: C
authors.lastname: Derks
authors.forename: Diana
authors.initials: D
authors.lastname: Cortes-Incio
authors.forename: Gabriele
authors.initials: G
authors.lastname: Linden
authors.forename: Silke
authors.initials: S
authors.lastname: Skottky
authors.forename: Peter
authors.initials: P
authors.lastname: Lütkes
authors.forename: Alexander
authors.initials: A
authors.lastname: Dechêne
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Peter
authors.initials: P
authors.lastname: Markus
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D055808:Drug Discovery; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Colorectal cancer; Lung cancer; Mutation; Personalised medicine; Profiling