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 Morganstein 67 yo man: PMH – Barrett’s/GERD and CAD, but EF good at 70% 8/2008: Stage III (T2N3) GE adenocarcinoma  neoadjuvant cisplatin/irinotecan + XRT  resection Late 2009: Lung mets confirmed on biopsy –HER2-positive (amplified = 4.0) –FOLFOX + trastuzumab, but poor tolerance to oxali  5-FU/LV + trastuzumab = response –Seen by cardiologist while on tx  EF  30% (global hypokinesis)  D/C all treatment –Follow up ECHO  still low EF

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

4. Case presented by Dr Morganstein 67 yo man: PMH – Barrett’s/GERD and CAD, but EF good at 70% 8/2008: Stage III (T2N3) GE adenocarcinoma  neoadjuvant cisplatin/irinotecan + XRT  resection Late 2009: Lung mets confirmed on biopsy –HER2-positive (amplified = 4.0) –FOLFOX + trastuzumab, but poor tolerance to oxali  5-FU/LV + trastuzumab = response –Seen by cardiologist while on tx  EF  30% (global hypokinesis)  D/C all treatment –Follow up ECHO  still low EF

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

6. Case presented by Dr Morganstein 67 yo man: PMH – Barrett’s/GERD and CAD, but EF good at 70% 8/2008: Stage III (T2N3) GE adenocarcinoma  neoadjuvant cisplatin/irinotecan + XRT  resection Late 2009: Lung mets confirmed on biopsy –HER2-positive (amplified = 4.0) –FOLFOX + trastuzumab, but poor tolerance to oxali  5-FU/LV + trastuzumab = response –Seen by cardiologist while on tx  EF  30% (global hypokinesis)  D/C all treatment –Follow up ECHO  still low EF

7. Copyright © 2011 Research To Practice. All rights reserved. Bang YJ et al. Lancet 2010;376(9742):687-97. Cardiac Safety of Trastuzumab + Chemotherapy versus Chemotherapy Alone in HER2-Positive Advanced Gastric or GE Junction Tumors Chemo Alone (n = 290) Chemo + T (n = 294) Cardiac Adverse Events (AEs) (All Grades) 6% Cardiac AEs (Grade 3/4) 3%1% Cardiac Failure<1% Cardiac Dysfunction (≥10% drop in LVEF to an absolute value <50%)* 1%5% * n = 187 for Chemo alone arm, n = 237 for Chemo + T arm

8. Copyright © 2011 Research To Practice. All rights reserved. Ongoing Phase II/III Trials: HER2-Positive Gastric Cancer Study Phase Target Accrual DesignStudy Endpoints Metastatic Gastric Cancer LOGiCIII 535 (open) CapeOx + lapatinib or placebo OS PFS ORR EORTC-40071II 192 (open) ECF/X +/- lapatinib OS PFS ORR NCT01191697II 36 (open) CapeOx + bevacizumab + trastuzumab ORR Operable Gastric Cancer NCT01130337II45 XELOX + trastuzumab DFS www.ClinicalTrials.gov, January 2011.

9. Copyright © 2011 Research To Practice. All rights reserved. Trastuzumab in Combination with Chemotherapy versus Chemotherapy Alone for Treatment of HER2-Positive Advanced Gastric or Gastro- Oesophageal Junction Cancer (ToGA): A Phase 3, Open-Label, Randomised Controlled Trial Bang YJ et al. Lancet 2010;376(9742):687-97.

10. Copyright © 2011 Research To Practice. All rights reserved. Case presented by Dr Morganstein 67 yo man: PMH – Barrett’s/GERD and CAD, but EF good at 70% 8/2008: Stage III (T2N3) GE adenocarcinoma  neoadjuvant cisplatin/irinotecan + XRT  resection Late 2009: Lung mets confirmed on biopsy –HER2-positive (amplified = 4.0) –FOLFOX + trastuzumab, but poor tolerance to oxali  5-FU/LV + trastuzumab = response –Seen by cardiologist while on tx  EF  30% (global hypokinesis)  D/C all treatment –Follow up ECHO  still low EF