1. Copyright © 2011 Research To Practice. All rights reserved. Faculty National GI Tumor Board Clinical Investigators Provide Their Perspectives on Current Cases of Gastrointestinal Cancer Friday, January 21, 2011 7:00 PM – 9:30 PM San Francisco, California Moderator Neil Love, MD Eileen M O’Reilly, MD Eric Van Cutsem, MD, PhD Andrew X Zhu, MD, PhD Charles D Blanke, MD David Cunningham, MD Steven A Curley, MD

2. Copyright © 2011 Research To Practice. All rights reserved. Case presented by Dr Polkinghorn 22 yo woman, married, teacher 7/2010: Abdominal pain  workup reveals cystic mass in pancreas and multiple hepatic lesions –Biopsy = pancreatic adenocarcinoma –FOLFIRINOX - no response, substantial toxicity Switched to gemcitabine and erlotinib –Again, substantial toxicity –Scans are “stable” in pancreas and liver mets, small  in spleen lesions BRCA testing - negative

3. Copyright © 2011 Research To Practice. All rights reserved.

4. Case presented by Dr Polkinghorn 22 yo woman, married, teacher 7/2010: Abdominal pain  workup reveals cystic mass in pancreas and multiple hepatic lesions –Biopsy = pancreatic adenocarcinoma –FOLFIRINOX - no response, substantial toxicity Switched to gemcitabine and erlotinib –Again, substantial toxicity –Scans are “stable” in pancreas and liver mets, small  in spleen lesions BRCA testing - negative

5. Copyright © 2011 Research To Practice. All rights reserved. Randomized Phase III Trial Comparing FOLFIRINOX versus Gemcitabine as First-Line Treatment for Metastatic Pancreatic Adenocarcinoma: Preplanned Interim Analysis Results of the PRODIGE 4/ACCORD 11 Trial Conroy T et al. Proc ASCO 2010;Abstract 4010.

6. Copyright © 2011 Research To Practice. All rights reserved. Conroy T et al. Proc ASCO 2010;Abstract 4010. Efficacy Parameter FOLFIRINOX (n = 171) Gemcitabine (n = 171) Hazard ratio (p-value) Disease control rate (CR + PR + SD) 70.2% (0.6% + 31% + 38.6%) 50.9% (0% + 9.4% + 41.5%) — (0.0003) Progression15.2%34.5%— Progression-free survival 6.4 months3.3 months 0.47 (<0.0001) Overall survival11.1 months6.8 months 0.57 (<0.0001) FOLFIRINOX recommended as new standard of care for metastatic pancreatic cancer with bilirubin <1.5 ULN and PS 0-1 PRODIGE 4/ACCORD 11: Efficacy Median follow-up: 26.6 months

7. Copyright © 2011 Research To Practice. All rights reserved. AE (% per patient) FOLFIRINOX (n = 167) Gemcitabine (n = 169)p-value Febrile neutropenia5.40.60.009 Thrombocytopenia9.12.40.008 Peripheral neuropathy9.000.0001 Vomiting14.54.70.002 Diarrhea12.71.20.0001 ALT7.318.60.0022 FOLFIRINOX regimen is more toxic, but toxicity is manageable PRODIGE 4/ACCORD 11: Selected Grade 3/4 Adverse Events (AE) Conroy T et al. Proc ASCO 2010;Abstract 4010.

8. Copyright © 2011 Research To Practice. All rights reserved. Faculty National GI Tumor Board Clinical Investigators Provide Their Perspectives on Current Cases of Gastrointestinal Cancer Friday, January 21, 2011 7:00 PM – 9:30 PM San Francisco, California Moderator Neil Love, MD Eileen M O’Reilly, MD Eric Van Cutsem, MD, PhD Andrew X Zhu, MD, PhD Charles D Blanke, MD David Cunningham, MD Steven A Curley, MD

9. Copyright © 2011 Research To Practice. All rights reserved. Case presented by Dr Polkinghorn 22 yo woman, married, teacher 7/2010: Abdominal pain  workup reveals cystic mass in pancreas and multiple hepatic lesions –Biopsy = pancreatic adenocarcinoma –FOLFIRINOX - no response, substantial toxicity Switched to gemcitabine and erlotinib –Again, substantial toxicity –Scans are “stable” in pancreas and liver mets, small  in spleen lesions BRCA testing - negative

10. Copyright © 2011 Research To Practice. All rights reserved. A phase II trial of nab-paclitaxel in patients with advanced pancreatic cancer who have progressed on gemcitabine-based therapy Hosein JP et al. Proc ASCO 2010;Abstract 4120.

11. Copyright © 2011 Research To Practice. All rights reserved. Hosein PJ et al. Proc ASCO 2010;Abstract 4120 Nab-paclitaxel monotherapy after gemcitabine based therapy Efficacy (n = 19) Time point (months)PFSOS 331.6%73.7% 615.8%57.9% 95.3%47.4% 125.3%36.8% Median1.6 months7.3 months

12. Copyright © 2011 Research To Practice. All rights reserved. Case presented by Dr Polkinghorn 22 yo woman, married, teacher 7/2010: Abdominal pain  workup reveals cystic mass in pancreas and multiple hepatic lesions –Biopsy = pancreatic adenocarcinoma –FOLFIRINOX - no response, substantial toxicity Switched to gemcitabine and erlotinib –Again, substantial toxicity –Scans are “stable” in pancreas and liver mets, small  in spleen lesions BRCA testing - negative