Abstract B93: A data base of N of 1 case reports from pancreatic cancer patients enrolled in First-in-man studies 2002 through 2012

Abstract

Abstract Background: First-in-man (FIM) studies test different doses of novel therapeutics for the first time in humans. The purpose of this work was to develop a data base with FIM studies published in the last decade and to identify extraordinary responses to therapy in patients with advanced pancreatic cancer. Methods: We conducted a search in Scopus of all FIM studies published between 2002 and 2012. We collected the following information: author, date and journal of publication, class of drug, route of administration, dose escalation design, patient demographic information, grade 3-4 toxicities, dose limiting toxicities, deaths during trial (including treatment related deaths), radiologic response, trial location and tumor types included in each trial. Results: We identified 3065 references through the Scopus search. Among these we found 118 FIM studies enrolling 5369 patients with advanced cancers from 2002 through 2012. The most common tumor types were colorectal cancer 1055 (19.6%), lung cancer 456 (8.4%), melanoma 475 (8.8%), breast cancer 319 (5.9%) and pancreatic ductal adenocarcinoma 296 (5.5%). There were 194 deaths including 17 (0.3%) treatment related deaths. 12 patients (0.2%) had complete response as best response to therapy including a patient with pancreatic cancer treated with bosutinib (a novel Src/abl tyrosin kinase inhibitor). 1 patient with pancreatic cancer had partial response to CHR-3996 (a novel histone deacetylase inhibitor) with a progression free survival (PFS) of 12 months. A second patient had a partial response to trametinib (MEK inhibitor) with a PFS of 11.75 months. Interestingly histone deacetylases are components of core signaling pathways in pancreatic cancer such Cell cycle and Notch pathway. Moreover, Src is commonly activated in pancreatic cancer. Conclusions: Novel approaches are urgently needed to treat pancreatic cancer. This includes identifying novel treatment opportunities through N of 1 case reports. We have retrospectively identified extraordinary responses to therapy in patients with advanced pancreatic enrolled in FIM studies with Src, HDAC and MEK inhibitors. Efforts should be now focused on understanding the underpinning biology of the disease in these patients. Citation Format: Ignacio Garrido-Laguna, Danielle Tometich, Kenneth Boucher, Sunil Sharma. A data base of N of 1 case reports from pancreatic cancer patients enrolled in First-in-man studies 2002 through 2012. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B93.