title: N of 1 case reports of exceptional responders accrued from pancreatic cancer patients enrolled in first-in-man studies from 2002 through 2012.
abstract: OBJECTIVE
  To identify exceptional responders among patients with advanced pancreatic cancer enrolled in first-in-man (FIM) studies.
  
  
  METHODS
  A Scopus search identified 66 FIM studies that enrolled at least one patient with advanced pancreatic cancer between 2002-2012. Descriptive statistics were used to summarize categorical variables. We also screened CRKL amplifications in the FoundationOne™ pancreatic cancer database.
  
  
  RESULTS
  Most FIM studies included targeted therapies (76 vs. 24%). The most common targeted therapy involved cell cycle inhibitors (24%). Pharmacodynamic analyses were more frequently done in trials with targeted therapies (70 vs. 31%, p=0.006). Response rates were similar. Treatment-related death was 0.5%. Skin, cardiovascular and metabolic grade 3-4 toxicities were more frequent with targeted therapies. Four exceptional responses were identified including a complete response to bosutinib (Src Inhibitor) and partial responses to trametinib (MEK inhibitor) (2 patients) and CHR-3996 (histone deacetylase inhibitor). We found that CRKL amplifications, a potential biomarker for Src inhibitors, are present in 1% of PDA.
  
  
  CONCLUSIONS
  We retrospectively identified extraordinary responses among patients with advanced PDA enrolled in FIM studies with Src, HDAC and MEK inhibitors. We identified CRKL amplifications are present in 1% of PDA and need to be evaluated as predictive biomarker for Src inhibitors.
authors.affiliation: Departments of Internal Medicine (Division of Oncology), Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City ; Center for Investigational Therapeutics, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garrido-Laguna
authors.affiliation: Departments of Internal Medicine (Division of Oncology), Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
authors.forename: Danielle
authors.initials: D
authors.lastname: Tometich
authors.affiliation: Oncological Sciences, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: Oncological Sciences, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
authors.forename: Jian
authors.initials: J
authors.lastname: Ying
authors.affiliation: Department of Pathology at Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
authors.forename: Katherine
authors.initials: K
authors.lastname: Geiersbach
authors.affiliation: Utah Cancer Specialists.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Whisenant
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts ; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Departments of Internal Medicine (Division of Oncology), Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City ; Center for Investigational Therapeutics, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
keywords: CRKL amplification; N of 1; first-in-man studies; pancreatic cancer