Abstract LB-221: Phase II study of therapy selected by molecular profiling in patients with previously treated metastatic pancreatic cancer. A study of the stand up to cancer (SU2C) consortium
Authors: Ramanathan Ramesh K. , Barrett Michael , Weiss Glen J. , Posner Richard , NV Rajeshkumar , Jameson Gayle , Demeure Michael , Hoering Antje , Stites Edward , Maitra Anirban , Fulk Monica , Hidalgo Manuel , Von Hoff Daniel D. 
Published: August 2012

Abstract
Background: A significant number of patients with refractory metastatic pancreatic cancer (mPC) have an adequate performance status (PS) and able to pursue subsequent therapy. However the outcome of salvage therapy is poor, there is no standard therapy and selection is empiric. We designed a phase II study to evaluate the efficacy of therapy selected by molecular profiling for mPC patients. Methods: Eligible patients had evidence of mPC, had progressive disease following at least one systemic therapy and a metastatic lesion amenable to percutaneous biopsy. All patients were required to have a KPS of &gt;70 and adequate bone marrow, kidney and liver function. The study required 35 evaluable patients, this design has a power of 86% for detecting a true one year survival rate of &gt; 20% versus the null hypothesis survival rate of &lt; 5%. Patients underwent a percutaneous biopsy, sample was fresh frozen, divided into 3 and sent for IHC, CGH and microarray (MA). Treatment selection was based on the Target Now® IHC assay (Caris Life Sciences, Irving, TX). For CGH analysis, flow sorted nuclei of diploid and aneuploid tumor cell populations were processed and hybridized to 400,000 feature CGH arrays. MA was matched to the NCI-60 cell line expression and the Pan-Xeno bank at Johns Hopkins University for drug sensitivity. Results: Forty nine subjects were accrued between August 2010-January 2012. There were no major complications due to biopsy. Fourteen patients did not start protocol therapy either due to insufficient tumor on biopsy or due to worsening cancer related symptoms after biopsy. The demographics of evaluable patients (n=34) are M/F (59%/41%), the majority had KPS of 70-80 and age range is 34-78 (median 62.5 years). Time from first diagnosis of mPC to biopsy ranged from 5.8-26.7 months (median 16.1 months). Patients had 1-6 prior regimens with a median of 2. The most common IHC targets were Topoisomerase 1 or 2 and Thymidylate synthase. Only commercially available agents were prescribed. Common regimens/ agents recommended were FOLFIRI, FOLFOX, irinotecan and doxorubicin. Conclusions: Study has completed accrual, one patient treated with FOLFIRI is a one year survivor. Genomic and pathway analysis is ongoing to understand response and molecular factors of patients with long term survival from first diagnosis. In most patients, molecular profiling resulted in at least 2 targets for therapy and a non cross resistant regimen could be implemented. (Supported by a SU2C- pancreatic dream team grant.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-221. doi:1538-7445.AM2012-LB-221