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Oncoscience. 2015 Mar 14;2(3):285-93. eCollection 2015.

N of 1 case reports of exceptional responders accrued from pancreatic cancer patients enrolled in first-in-man studies from 2002 through 2012.

Author information

  • 1Departments 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.
  • 2Departments of Internal Medicine (Division of Oncology), Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
  • 3Oncological Sciences, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
  • 4Department of Pathology at Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City.
  • 5Utah Cancer Specialists.
  • 6Foundation Medicine, Cambridge, Massachusetts.
  • 7Foundation Medicine, Cambridge, Massachusetts ; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA.

Abstract

PURPOSE:

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 FoundationOneā„¢ 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.

KEYWORDS:

CRKL amplification; N of 1; first-in-man studies; pancreatic cancer

PMID:
25897431
PMCID:
PMC4394134
DOI:
10.18632/oncoscience.141
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