N of 1 case reports of exceptional responders accrued from pancreatic cancer patients enrolled in first-in-man studies from 2002 through 2012
Ignacio Garrido-Laguna1,2, Danielle Tometich1, Nan Hu3 , Jian Ying3, Katherine Geiersbach4, Jonathan Whisenant5, Kai Wang6, Jeffrey S. Ross6,7 and Sunil Sharma1,2
1 Departments of Internal Medicine (Division of Oncology), Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City
2 Center for Investigational Therapeutics, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City
3 Oncological Sciences, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City
4 Department of Pathology at Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City
5 Utah Cancer Specialists
6 Foundation Medicine, Cambridge, Massachusetts
7 Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA
Ignacio Garrido-Laguna, email:
Keywords: N of 1, first-in-man studies, pancreatic cancer, CRKL amplification
Received: December 03, 2014 Accepted: March 04, 2015 Published: March 14, 2015
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 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.