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

CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS 7
Pipeline overview 7
Drugs in late-phase development for NSCLC 7
Drugs in Phase II development for NSCLC 8
Drugs in Phase I development for NSCLC 12
Pipeline by development phase and therapy class 12
There are over 100 drugs in the NSCLC pipeline, more than half of which are molecular targeted therapies 12
Pipeline by mode of action 15
Pipeline drugs have diverse modes of action 15
Pipeline by indication 17
The majority of drugs are being investigated in the first-line treatment of advanced disease 17
Pipeline by company 18
Nearly 100 different companies or institutions are involved in the NSCLC pipeline 18
Merck Serono is the only company with two drugs in Phase III development for NSCLC 19
Top three companies in terms of the number of NSCLC pipeline candidates are Pfizer, Novartis and Bristol-Myers Squibb 21
Pfizer 21
Novartis 23
Bristol Myers Squibb 25
Key metrics 26
Datamonitor pipeline assessment summary 30

CHAPTER 3 NON-SMALL CELL LUNG CANCER - MARKET POTENTIAL 34
Definition of NSCLC 34
Non-small cell lung cancer accounts for about 80% of all lung cancers 34
Three major types of NSCLC exist 35
Staging of NSCLC is usually based on the AJCC Tumor Node Metastases (TNM) staging system 36
A revised staging system may have treatment implications in the future 37
The NSCLC market is segmented according to disease stage 37
Risk factors in the development of NSCLC 38
Overview of NSCLC treatment 38
The treatment of early-stage disease (Stages I-IIIA) 40
The management of early-stage disease is largely based on surgery 40
Adjuvant chemotherapy may benefit a subset of patients with early-stage disease 41
Radiotherapy has a central role in the treatment of unresectable early-stage disease 42
The treatment of advanced disease (Stages IIIB-IV) 42
Chemoradiotherapy is the standard of care in patients with unresectable Stage IIIB disease 43
A recent trial has generated controversy regarding the use of consolidation chemotherapy in unresectable Stage III disease 43
Systemic platinum-based chemotherapy has a central role in the management of advanced disease 44
The addition of Avastin may offer an added advantage for a subset of patients 44
A number of options are available for previously-treated patients 45
The role of targeted therapies in the treatment of NSCLC 46
Avastin is extensively used in the first-line setting, but only a subset of patients is eligible for treatment 46
Off-label use of Tarceva is taking place in the first-line setting 49
AstraZeneca will be seeking EU approval for Iressa in the second-line setting 51
Targeted therapies may find an application in a number of settings in NSCLC 53
The treatment of NSCLC is moving into an era of individualized medicine 53
The epidemiology of NSCLC 55
There will be more than 380,000 new cases of NSCLC in the seven major markets in 2017 55
Mortality from NSCLC is high 55
NSCLC is predominantly a disease of the elderly 56
Adenocarcinoma has become the most common histological subtype of NSCLC 56
Asia will face a major epidemic of lung cancer in the future 57
NSCLC incidence and mortality rates are still increasing in women 57
NSCLC in never-smokers may become more prevalent in the future 57
Increased detection by screening is unlikely to affect NSCLC incidence 58
NSCLC is an attractive market for new product development 58
Unmet need in NSCLC 60
Effective treatments are required for both advanced and early-stage disease 60
NSCLC needs to be recognized as a heterogeneous disease 60
Less toxic treatments for poor performance status patients are required 61
The treatment of NSCLC is in need of an overall refinement 61

CHAPTER 4 R&D APPROACH 63
Classification of pipeline products 63
Cytotoxic therapies 63
Molecular targeted therapies 64
Single-target signal transduction inhibitors 65
Angiogenesis inhibitors 65
Apoptosis inducers 65
Cell cycle inhibitors 65
Multi-targeted inhibitors 66
Epigenetic modulators 66
Immunotherapeutic agents 66
Evolution in NSCLC clinical trial design 67
The heterogeneity of NSCLC makes patient selection a critical issue 67
Targeted trial designs utilizing biomarkers are increasingly used 68
Early-phase clinical trials and endpoints may need redefining 69
Barriers may still exist to the accrual of patients to NSCLC trials 70
NSCLC trials may not be very representative of the clinical setting 71

CHAPTER 5 MOLECULAR TARGETED THERAPIES ANALYSIS AND FORECASTS 72
Overview of molecular targeted therapies 72
Pipeline summary 72
Late-phase pipeline of molecular targeted therapies 74
Phase II pipeline of molecular targeted therapies 74
Phase I pipeline of molecular targeted therapies 77
Comparative forecasts 77
Definition of current comparator therapy 78
Avastin (bevacizumab Genentech/Roche/Chugai) 78
Erbitux (cetuximab; ImClone/Merck Serono/Bristol-Myers Squibb) 79
Drug overview 79
Key historical events 80
Clinical development in NSCLC 82
Phase III study of Erbitux with cisplatin and vinorelbine meets its primary endpoint of improved survival 84
Phase III study of Erbitux with carboplatin and a taxane fails to meet its primary endpoint 86
A number of other trials have evaluated Erbitux in NSCLC 89
A combination of chemotherapy, Erbitux, and Avastin is being evaluated 91
Erbitux may enhance the efficacy of chemoradiotherapy in the treatment of unresectable, locally advanced disease 91
Datamonitor comments 93
Erbitux may become the first EGFR inhibitor to show a survival improvement in combination with chemotherapy in the first-line setting 93
The extent to which US physicians will adopt the cisplatin/vinorelbine regimen may affect Erbitux's uptake 93
Erbitux may achieve a higher uptake in patients who are not eligible for Avastin treatment 94
Erbitux could find additional application in the treatment of locally advanced, unresectable NSCLC 95
Forecasts to 2017 95
Nexavar (sorafenib; Bayer Schering) 97
Drug overview 97
Key historical events 97
Clinical development in NSCLC 98
The combination of Nexavar with platinum-based chemotherapy fails to improve overall survival in a Phase III study 100
Nexavar monotherapy results in disease stabilization in the second and third-line settings 101
An additional study has evaluated Nexavar monotherapy in the second-line setting 103
Datamonitor comments 104
Nexavar's potential in NSCLC now significantly limited 104
Nexavar joins the growing number of TKIs that have failed in the first-line setting 104
Bayer Schering has adopted a 'conservative' strategy for Nexavar's Phase III trial with Gemzar and cisplatin 105
Forecasts to 2017 106
Recentin (cediranib; AstraZeneca) 108
Drug overview 108
Key historical events 109
Clinical development in NSCLC 110
Two Phase I trials have evaluated Recentin in the first-line treatment of advanced NSCLC 111
Datamonitor comments 112
Recentin fails to progress into Phase III in advanced NSCLC 112
Sutent (sunitinib; Pfizer) 112
Drug overview 112
Key historical events 113
Clinical development in NSCLC 113
Sutent monotherapy shows moderate clinical activity in the second- and third-line setting of advanced NSCLC 115
The combination of Sutent with Gemzar and cisplatin is safe and tolerable 116
Datamonitor comments 117
The toxicity and cost of adding Sutent to Tarceva will need to be justified 117
Targeting the second-line setting may be a successful strategy for Sutent 118
Forecasts to 2017 118
Zactima (vandetanib; AstraZeneca) 120
Drug overview 120
Key historical events 121
Clinical development in NSCLC 122
The addition of Zactima to platinum-based chemotherapy improves progression-free survival in the first-line setting 123
The combination of Zactima with Taxotere and with Iressa improves progression-free survival in the second-line setting 124
Datamonitor comments 127
Zactima's multi-targeted nature could offer a competitive advantage 127
Zactima is targeting a broad population of previously-treated, advanced NSCLC patients 127
The head-to-head trial against Tarceva is a high-risk strategy 128
AstraZeneca's strength in the oncology market will be key to Zactima's success 129
Forecasts to 2017 129
Zolinza (vorinostat; Merck & Co) 131
Drug overview 131
Key historical events 132
Clinical development in NSCLC 132
Zolinza shows moderate clinical activity as a second-line monotherapy in NSCLC 134
A Phase II trial of Zolinza with Tarceva in relapsed/refractory NSCLC was terminated 135
Zolinza shows preliminary evidence of clinical activity in combination with chemotherapy 135
Datamonitor comments 135
A different strategy may have improved Zolinza's chances of success in the NSCLC market 135
Forecasts to 2017 136
Aflibercept (VEGF-Trap; Sanofi Aventis/Regeneron) 138
Drug overview 138
Key historical events 138
Clinical development in NSCLC 139
Aflibercept shows manageable toxicity and some evidence of clinical activity in heavily pre-treated, advanced NSCLC patients 139
Datamonitor comments 140
The combination of aflibercept with Taxotere will have to demonstrate a favorable toxicity profile 140
Aflibercept's Phase III trial may not be accounting for the current standards of care 141
Aflibercept's Phase II trial results are interpreted using the modified RECIST criteria 141
Presence in oncology field will aid commercialization of aflibercept 142
Forecasts to 2017 142
BIBW 2992 (Boehringer Ingelheim) 144
Drug overview 144
Key historical events 144
Clinical development in NSCLC 145
Phase III study will evaluate BIBW 2992 in patients who have failed prior therapy with reversible EGFR inhibitors 145
BIBW 2992 shows preliminary evidence of activity in a Phase I study in solid malignancies 146
Datamonitor comments 147
Targeting patients who are Tarceva-refractory may be a successful entry strategy into the NSCLC market 147
Motesanib (AMG706; Amgen/Takeda Pharmaceutical) 148
Drug overview 148
Key historical events 148
Clinical development in NSCLC 148
The combination of motesanib with chemotherapy is safe and shows preliminary evidence of clinical activity 149
Datamonitor comments 150
Can motesanib succeed where other tyrosine kinase inhibitors have failed? 150
Amgen runs a high risk with the inclusion of squamous cell patients in motesanib's Phase III trial 151
Forecasts to 2017 151

CHAPTER 6 CYTOTOXIC THERAPIES ANALYSIS AND FORECASTS 154
Overview of cytotoxic therapies 154
Pipeline summary 154
Late-phase pipeline of cytotoxic therapies 155
Phase II pipeline of cytotoxic therapies 156
Phase I pipeline of cytotoxic therapies 157
Comparative forecasts 158
Definition of current comparator therapy 159
Taxotere (docetaxel; Sanofi-Aventis) 159
Abraxane (albumin-bound paclitaxel; Abraxis) 159
Drug overview 159
Key historical events 160
Clinical development in NSCLC 161
The combination of Abraxane with carboplatin and Avastin is well-tolerated 162
Abraxane shows clinical activity and a favorable toxicity profile as a first-line monotherapy in metastatic NSCLC 163
Datamonitor comments 164
A novel taxane with an improved toxicity profile could gain a share of the NSCLC market 164
There is a high chance of approval for Abraxane in NSCLC 165
Abraxane's sales growth in the breast cancer market may be indicative of an uptake in NSCLC 166
Forecasts to 2017 166
Glutoxim (NOV-002; Novelos) 168
Drug overview 168
Key historical events 168
Clinical development in NSCLC 169
Glutoxim has been evaluated in the first-line treatment of advanced NSCLC 169
Datamonitor comments 170
Glutoxim's clinical and commercial potential cannot be evaluated 170
Forecasts to 2017 171
Javlor (vinflunine; Pierre Fabre) 173
Drug overview 173
Key historical events 173
Clinical development in NSCLC 173
Javlor shows efficacy equivalent to that of Taxotere in a Phase III trial in advanced NSCLC 174
Datamonitor comments 176
Pierre Fabre's intentions for Javlor in NSCLC are unclear 176
Javlor will face intense competition in the second-line setting 176
Javlor could increase its uptake with use in combination with radiotherapy 176
Forecasts to 2017 177
Lipoplatin (liposomal cisplatin; Regulon) 179
Drug overview 179
Key historical events 179
Clinical development in NSCLC 179
The combination of Lipoplatin with Gemzar is safe and shows evidence of clinical activity 180
Lipoplatin shows a better toxicity profile than cisplatin as part of a combination regimen with paclitaxel 181
Datamonitor comments 182
Favorable market conditions exist for novel cytotoxic agents such as Lipoplatin 182
A more experienced oncology player could improve Lipoplatin's chances of success in the market 183
Forecasts to 2017 183
Taxoprexin (DHA paclitaxel; Luitpold) 185
Drug overview 185
Key historical events 185
Clinical development in NSCLC 186
Taxoprexin shows moderate clinical efficacy and an unfavorable toxicity profile in a Phase II trial 186
Datamonitor comments 187
Taxoprexin's clinical results to date raise concerns regarding its future in the NSCLC market 187
Forecasts to 2017 188
Xyotax (paclitaxel polyglumex; Cell Therapeutics/Novartis) 190
Drug overview 190
Key historical events 191
Clinical development in NSCLC 191
Three Phase III trials failed to meet their primary endpoints of improved overall survival 192
Combined analysis of STELLAR 3 and STELLAR 4 showed a survival benefit in women 194
Datamonitor comments 195
Non-inferiority may grant Xyotax approval in an underserved patient population with poor prognosis 195
It is unclear whether Cell Therapeutics will achieve a return on Xyotax's development costs 196
The use of a prognostic biomarker for the selection of patients could enhance Xyotax's clinical results 196
Forecasts to 2017 196

CHAPTER 7 IMMUNOTHERAPIES ANALYSIS AND FORECASTS 199
Overview of immunotherapies 199
Pipeline summary 199
Late-phase pipeline of immunotherapies 200
Phase II pipeline of immunotherapies 201
Phase I pipeline of immunotherapies 202
Comparative forecasts 203
Definition of current comparator therapy 204
Stimuvax (BLP-25; Merck Serono) 204
Drug overview 204
Key historical events 205
Clinical development in NSCLC 205
Stimuvax shows evidence of a survival benefit in patients with Stage IIIB locoregional disease 206
Datamonitor comments 208
The need for a minimally toxic maintenance therapy may drive Stimuvax's uptake 208
Stimuvax may have to overcome regulatory hurdles... 208
Forecasts to 2017 209
MAGE-A3 ASCI (GSK1572932A; GlaxoSmithKline) 211
Drug overview 211
Key historical events 212
Clinical development in NSCLC 212
MAGE-A3 ASCI decreases the risk of cancer recurrence after surgery in a Phase II trial 213
Datamonitor comments 214
An adjuvant therapy with a favorable toxicity profile would be welcome in the NSCLC market 214
Recruitment to the large Phase III trial may present challenges 215
MAGE-A3 needs to overcome regulatory and pharmacoeconomic obstacles 215
Forecasts to 2017 216

APPENDIX 218

Bibliography 218
List of tables 237
List of figures 238
List of abbreviations 239
Contributing experts 241
Methodology 241
Datamonitor forecast methodology 241
Epidemiology forecasts 241
Product forecasts 241
Datamonitor drug assessment summary 242
About Datamonitor 244
About Datamonitor Healthcare 245
Datamonitor Healthcare's therapy area capabilities 245
About the Disease Analysis Team 246
Disclaimer 24