Contents:

CHAPTER 1 KEY FINDINGS 3 INTRODUCTION 9 Scope 9 CHAPTER 2 KEY EVENTS IN THE LUNG CANCER MARKET IN Q1 2004 11 Introduction 11 Tarceva aiming for second-line approval 11 Rolling submission of NDA 12 Treading a similar path to Iressa 12 Potential in other indications? 13 Tarceva plus Avastin? 15 Erbitux could enter the frame 15 Herceptin’s failure in lung cancer 17 Herceptin for NSCLC 17 Synergy of HER-2 and EGF 18 Phase III trial for Sarasar halted 19 Encouraging results in Phase I/II trials 19 Difficult road ahead for FTIs 20 Approval of Alimta for mesothelioma 21 Clinical advantages of Alimta 21 A bigger potential in NSCLC 23 CHAPTER 3 EGFR INHIBITORS – PRODUCTS TO TRANSFORM THE LUNG CANCER MARKET? 24 Overview of EGFR in cancer 24 The role of EGFR in cancer 24 CHAPTER 4 ANALYSIS OF KEY FINDINGS FROM INTACT I AND II TRIALS FOR IRESSA IN COMBINATION WITH CHEMOTHERAPY 30 Iressa’s approval for the treatment of NSCLC 30 INTACT 1 and INTACT 2 trials of Iressa in NSCLC 31 Why the differences between IDEAL and INTACT? 34 CHAPTER 5 REDEFINING THE STRATEGY FOR EGFR INHIBITION – RIGHT PLACE AT THE RIGHT TIME 35 Lessons from Glivec (imatinib) 35 Predicting response to EGFR inhibitors 36 Cost of EGFR inhibitors 37 CHAPTER 6 MARKET POTENTIAL AND PHYSICIAN OPINION OF INNOVATIVE AGENTS IN NSCLC 39 High incidence and low survival in NSCLC 39 Iressa, first to market, but a clutch of new drugs on the horizon 42 CHAPTER 7 FUTURE TRENDS FOR USE OF INNOVATIVE AGENTS IN NSCLC 45 Japan: Iressa’s first market 45 FDA approval for third-line treatment only – for now 45 EU approval imminent for third-line therapy 45 Increasing competition from other targeted therapies 46 Future expansion of indication to include adjuvant therapy 47 Targeted therapies further fragment cancer market 48 CHAPTER 8 THE COLORECTAL CANCER JIGSAW PUZZLE: WHERE DO INNOVATIVE THERAPIES FIT? 50 New therapies, though welcome, will increase the complexity of decisions facing oncologists. Clinical decisions must be clearly signposted, or oncologists will continue along well-trodden paths 52 The first EGFR inhibitor makes it to market… 52 …but how should it be used? 54 A long road ahead, but what do prescribers do now? 55 And what of Avastin? 56 APPENDIX 58 References 58