ABOUT DATAMONITOR HEALTHCARE 2
About the Oncology pharmaceutical analysis team 2

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the cancer market 3
Related reports 5
Upcoming reports 6

CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS 8
Pipeline overview 8
Late-phase pipeline 8
Pipeline by indication 10
Melanoma emerges as the most popular R&D target, due to a significant level of unmet need which could result in high commercial reward 10

CHAPTER 3 R&D APPROACH 12
Classification of pipeline products 12
Cytotoxics 12
Molecular targeted therapies 13
Immunotherapeutic agents 15
Oncology clinical trial design 15

CHAPTER 4 COLORECTAL CANCER 17
Overview of colorectal cancer 17
Definition 17
Colorectal cancer is the third most common tumor type and cause of cancer-related death in both men and women 17
Epidemiology 18
Incidence continues to rise with an increase in prevalence of risk factors and the aging population 18
Mortality from colorectal cancer is relatively high due to a tendency for later diagnosis 18
Treatment of colorectal cancer 19
Unmet need in colorectal cancer 21
Summary of unmet needs 21
Lack of identifiable risk factors and effective screening tools 22
Prognosis remains poor, despite significant advances in therapy 22
A high rate of disease recurrence illustrates the need for more effective therapies 23
Pipeline overview 23
Definition of current comparator therapy 23
Pipeline summary 24
Late-phase pipeline 26
Phase II pipeline 26
Comparative forecasts 29
Pipeline candidates 32
Afinitor (everolimus; Novartis) 32
Drug overview 32
Key historical events 32
Clinical development in colorectal cancer 33
Datamonitor comments 34
Recentin (cediranib; AstraZeneca) 35
Drug overview 35
Key historical events 36
Clinical development in colorectal cancer 36
Datamonitor comments 38
Sutent (sunitinib; Pfizer) 40
Drug overview 40
Key historical events 40
Clinical development in colorectal cancer 41
Datamonitor comments 43
Aflibercept (VEGF-Trap; Regeneron/Sanofi-Aventis) 44
Drug overview 44
Key historical events 45
Clinical development in colorectal cancer 45
Datamonitor comments 48
Brivanib (BMS-582664; Bristol-Myers Squibb) 49
Drug overview 49
Key historical events 49
Clinical development in colorectal cancer 49
Datamonitor comments 51
Davanat (carbohydrate polymer drug delivery system; Pro-Pharmaceuticals) 52
Drug overview 52
Key historical events 52
Clinical development in colorectal cancer 53
Datamonitor comments 56
Satisfaction of unmet needs 58
Aflibercept and brivanib could eventually provide effective alternative therapies in metastatic colorectal cancer 58

CHAPTER 5 GASTRIC CANCER 59
Overview of gastric cancer 59
Definition 59
Gastric cancer is the second most common tumor type on a global scale 59
Epidemiology 60
Despite a worldwide decline in incidence, gastric cancer remains a major health burden 60
Mortality is a greater concern in the US and Western Europe 61
Treatment of gastric cancer 63
Unmet need in gastric cancer 65
Summary of unmet needs 65
Lack of effective systemic therapy 65
Poorly defined standard treatment regimens 66
Poor control of distant metastases 66
Complete lack of second-line options 67
Pipeline overview 67
Definition of current comparator therapy 67
Pipeline summary 68
Late-phase pipeline 69
Phase II pipeline 69
Comparative forecasts 71
Pipeline candidates 73
Avastin (bevacizumab; Genentech/Roche/Chugai) 73
Drug overview 73
Key historical events 73
Clinical development in gastric cancer 74
Datamonitor comments 77
Erbitux (cetuximab; ImClone/Bristol-Myers Squibb/Merck Serono) 79
Drug overview 79
Key historical events 79
Clinical development in gastric cancer 80
Datamonitor comments 85
Tykerb (lapatinib; GlaxoSmithKline) 85
Drug overview 85
Key historical events 86
Clinical development in gastric cancer 86
Datamonitor comments 88
Satisfaction of unmet needs 89
The three targeted therapies in late-phase development for gastric cancer show promise in fulfilling unmet need if certain hurdles can be overcome 89

CHAPTER 6 HEPATOCELLULAR CARCINOMA 91
Overview of hepatocellular carcinoma 91
Definition 91
Hepatitis is a known risk factor for hepatocellular carcinoma 91
Epidemiology 91
Japan accounts for nearly half of all new hepatocellular carcinoma cases in the seven major markets due to a high prevalence of hepatitis 91
Mortality from hepatocellular carcinoma is high, although prognosis is steadily improving 92
Treatment of hepatocellular carcinoma 93
Unmet need in hepatocellular carcinoma 95
Summary of unmet needs 95
Better systemic therapy is required 95
Clinical trials are currently poorly designed 96
HCC suffers from a relatively modest R&D interest 97
Pipeline overview 97
Definition of current comparator therapy 97
Pipeline summary 98
Late-phase pipeline 99
Phase II pipeline 99
Comparative forecasts 101
Pipeline candidates 104
Sutent (sunitinib; Pfizer) 104
Drug overview 104
Key historical events 104
Clinical development in hepatocellular carcinoma 104
Datamonitor comments 107
ThermoDox (heat-activated doxorubicin; Celsion) 109
Drug overview 109
Key historical events 109
Clinical development in hepatocellular carcinoma 110
Datamonitor comments 110
Miriplatin (SM-11355; Dainippon Sumitomo) 111
Drug overview 111
Key historical events 112
Clinical development in hepatocellular carcinoma 112
Datamonitor comments 113
Litx (talaporfin; Light Sciences Oncology) 114
Drug overview 114
Key historical events 115
Clinical development in hepatocellular carcinoma 115
Datamonitor comments 116
Satisfaction of unmet needs 117
Sutent could provide an effective alternative to Nexavar, however, the remaining pipeline drugs face significant barriers to market entry 117

CHAPTER 7 MELANOMA 118
Overview of melanoma 118
Definition 118
Melanoma is the least common type of skin cancer, although the most potentially fatal 118
Epidemiology 118
Incidence of melanoma will continue to rise due to increasing exposure of the population to UV light 118
Mortality from melanoma is relatively low in comparison to its incidence due to a high rate of early diagnosis 119
Treatment of melanoma 121
Unmet need in melanoma 123
Summary of unmet needs 123
Current therapeutics have a high risk-to-benefit ratio 123
Over the past three decades there have been few significant advances in drug therapy for metastatic disease 124
Early diagnosis is the key to curative treatment 124
Gene profiling will help individualize treatment approaches 124
Pipeline overview 125
Definition of current comparator therapy 125
Pipeline summary 126
Late-phase pipeline 128
Phase II pipeline 128
Comparative forecasts 132
Pipeline candidates 134
Genasense (oblimersen; Genta) 134
Drug overview 134
Key historical events 135
Clinical development in melanoma 136
Datamonitor comments 138
Elesclomol (STA-4783; Synta/GlaxoSmithKline) 139
Drug overview 139
Key historical events 139
Clinical development in melanoma 140
Datamonitor comments 142
Taxoprexin (DHA paclitaxel; Luitpold Pharmaceutical) 143
Drug overview 143
Key historical events 143
Clinical development in melanoma 143
Datamonitor comments 146
PEG-Intron (pegylated interferon-alpha; Schering-Plough) 147
Drug overview 147
Key historical events 147
Clinical development in melanoma 148
Datamonitor comments 149
Ipilimumab (MDX-010; Medarex/Bristol-Myers Squibb) 150
Drug overview 150
Key historical events 150
Clinical development in melanoma 151
Datamonitor comments 156
MDX-1379 (Medarex/Bristol-Myers Squibb) 157
Drug overview 157
Key historical events 157
Clinical development in melanoma 158
Datamonitor comments 159
Allovectin-7 (velimogene aliplasmid; Vical) 160
Drug overview 160
Key historical events 160
Clinical development in melanoma 161
Datamonitor comments 163
Satisfaction of unmet needs 163
The late-phase targeted therapies are most likely to fulfill unmet needs in melanoma, however, only if certain issues can be overcome 163

CHAPTER 8 PANCREATIC CANCER 165
Overview of pancreatic cancer 165
Definition 165
Pancreatic cancer represents a major health issue in the developed world 165
Epidemiology 165
Incidence of pancreatic cancer will continue to rise as a reflection of the aging population 165
Mortality from pancreatic cancer is nearly equal to its incidence 166
Treatment of pancreatic cancer 167
Unmet need in pancreatic cancer 168
Summary of unmet need 168
Associated with exceptionally poor survival rates 169
Earlier rates of diagnosis are desperately needed in order to boost survival 169
A lack of effective systemic therapies exists, therefore an higher level of R&D interest is needed 169
Pipeline overview 170
Definition of current comparator therapy 170
Pipeline summary 170
Late-phase pipeline 172
Phase II pipeline 172
Comparative forecasts 175
Pipeline candidates 178
Aflibercept (VEGF-Trap; Regeneron/Sanofi-Aventis) 178
Drug overview 178
Key historical events 178
Clinical development in pancreatic cancer 179
Datamonitor comments 180
Axitinib (AG-13736; Pfizer) 181
Drug overview 181
Key historical events 181
Clinical development in pancreatic cancer 182
Datamonitor comments 183
Larotaxel (XRP-9881; Sanofi-Aventis) 184
Drug overview 184
Key historical events 184
Clinical development in pancreatic cancer 185
Datamonitor comments 186
GV-1001 (tertomotide; Pharmexa) 187
Drug overview 187
Key historical events 187