Introduction
 
Pancreatic adenocarcinoma is the fifth leading cancer-related cause of death and is thus a major health issue in the developed world. Its aggressive nature and resistance to conventional therapy results in an exceedingly poor prognosis, with incidence and age-adjusted mortality rates nearly equivalent.
 

 
Scope
 
Diagnosis patterns of pancreatic adenocarcinoma, including stage distribution, extent of resectability and physician types responsible for diagnosis
 
Analysis of treatment modalities and regimens based on a survey of 182 clinical oncologists and surgeons across the seven major markets
 
Percentage of patients enrolled in clinical trials, outcomes of various treatment modalities and key physician prescribing influences
 
Late-phase pipeline analysis plus insight from interviews with key opinion leaders
 
Highlights
 
For the foreseeable future, gemcitabine will remain gold-standard treatment for pancreatic adenocarcinoma and retain its status as market leader. Despite an active late-phase pipeline, no agent is seriously threatening gemcitabine's position. Commercial potential will be increased if benefit is demonstrated in combination with gemcitabine.
 

 
As a result of exceedingly poor survival rates and a lack of effective treatment options, a major gap in the market exists for reliable and accurate diagnostics to facilitate screening and increase rates of early diagnosis of pancreatic adenocarcinoma. Any company willing to enter this area will be met with a risky, but lucrative opportunity.
 

 
Due to low perceived patient potential, pancreatic adenocarcinoma has not traditionally been the focus of clinical trial activity. As a result, discrepancies exist over optimal treatment modalities and regimens. However, this conflict is slowly being resolved with clinical trial data and the advent of molecular targeted therapies.
 

 
Reasons to Purchase
 
Identify physician types responsible for diagnosis and the key prescribing factors that influence prescription patterns for systemic therapy
 
Examine the significant unmet need within pancreatic adenocarcinoma and identify opportunities for new product development
 
Enhance commercial positioning by increasing understanding of current dynamics within the pancreatic adenocarcinoma market
 

TABLE OF CONTENTS
 
About the Oncology pharmaceutical analysis team 2
 
Richard Faint – Director of Oncology 2
 
CHAPTER 1 EXECUTIVE SUMMARY 3
 
Scope of the analysis 3
 
Datamonitor insight into the pancreatic adenocarcinoma market 4
 
Eli Lilly’s (Gemzar) gemcitabine remains the gold-standard treatment for pancreatic adenocarcinoma and will retain its status as market leader for the foreseeable future. Despite a comparatively active late-phase pipeline, no agent demonstrates the necessary characteristics to compete with gemcitabine viably. However, investigation of agents in combination with gemcitabine will increase commercial potential if survival benefit is demonstrated. 4
 
Datamonitor primary research shows that adjuvant chemotherapy is the treatment modality of choice for resectable pancreatic adenocarcinoma. Clinical trial results have demonstrated the detrimental effect of radiotherapy on cytotoxic activity within this setting, while there is a lack of data to support administration of neoadjuvant therapy. However, this latter modality does have significant advantages in comparison with adjuvant therapy, confirmation of which will arise from the ongoing Southwest Oncology Group, Eastern Cooperative Oncology Group and Radiation Therapy Oncology Group R9704 clinical trial, which is comparing neoadjuvant with adjuvant therapy. 6
 
First-line gemcitabine monotherapy is the favored treatment modality for non-resectable pancreatic adenocarcinoma according to Datamonitor primary research. French physicians appear particularly taken by the GEMOX regimen (gemcitabine with oxaliplatin), which is also growing in popularity across the European markets, despite being in Phase III clinical trials and used off-label. However, the regimen’s use remains low in other markets, where physician prescription patterns are influenced by other factors, such as national recommendations and guidelines. 7
 
Though incidence of pancreatic adenocarcinoma is relatively low, estimated at 82,240 across the seven major pharmaceutical markets in 2004, the disease continues to be plagued by exceedingly poor survival rates and a lack of effective treatment options. A major gap exists in the market for a reliable and accurate diagnostic to facilitate screening and early diagnosis of pancreatic adenocarcinoma, which would increase the potential of curative treatment and greatly improve prognosis. 9
 
Key metrics 11
 
CHAPTER 2 INTRODUCTION AND SCOPE 23
 
Coverage of the Stakeholder Insight Survey 23
 
Disease definition & epidemiology 23
 
Diagnosis 23
 
Resectable disease 23
 
Non-resectable disease 24
 
Key prescribing influences 24
 
CHAPTER 3 COUNTRY TREATMENT TREES 26
 
US 27
 
Japan 29
 
France 31
 
Germany 33
 
Italy 35
 
Spain 37
 
UK 39
 
CHAPTER 4 DEFINITION AND EPIDEMIOLOGY 41
 
Disease definition and classification 41
 
The pancreas 41
 
Pancreatic adenocarcinoma 42
 
Risk factors 42
 
Symptoms 43
 
Diagnosis 44
 
Staging 44
 
Epidemiology of pancreatic cancer 45
 
CHAPTER 5 DIAGNOSIS AND STAGING 47
 
Diagnosis 47
 
Physician types responsible for diagnosis 47
 
Surgeons and gastroenterologists diagnose most patients, while clinical oncologists serve a limited role 48
 
Primary care physicians of importance in Japan 49
 
Internists of importance in Spain 49
 
Other physician types also of relevance 49
 
Staging 50
 
Percentage of patients diagnosed at each stage 50
 
Highest proportion of patients diagnosed in late stages 51
 
Highest rates of early diagnosis in the UK and US 52
 
Extent of resection 52
 
Stage I 53
 
Stage IIA 54
 
Stage IIB 55
 
Stage III 56
 
Stage IV 57
 
Resectable versus non-resectable disease 58
 
Non-resectability increases with stage of disease 58
 
Highest proportion of resectable patients in Japan 58
 
Lowest proportion of resectable patients in the US and the UK 59
 
CHAPTER 6 TREATMENT OF RESECTABLE DISEASE 60
 
Treatment modalities 60
 
Adjuvant therapy most commonly employed 61
 
Benefit of neoadjuvant and adjuvant therapy together is unclear 62
 
Morbidity raises level of patients foregoing further cancer-direct therapy 63
 
Neoadjuvant treatment 63
 
Neoadjuvant drug therapy with or without radiotherapy used most 65
 
Limited role of neoadjuvant radiotherapy alone 66
 
Lowest use of radiotherapy in Italy and Japan 66
 
Most patients undergoing combination drug and radiotherapy in France 66
 
Highest rate of radiotherapy alone in the US 66
 
Adjuvant treatment 67
 
Adjuvant drug therapy alone appears to be standard 68
 
Low rates of radiotherapy use in adjuvant setting 69
 
UK and Japan have the lowest rates of radiotherapy use 69
 
Radiotherapy most popular in the US 70
 
CHAPTER 7 TREATMENT OF NON-RESECTABLE DISEASE 71
 
Treatment modalities 71
 
Preferred modality is first-line drug therapy alone… 72
 
…though trials have shown superiority of multi-modality treatment 72
 
Justification for first-line drug therapy alone 73
 
Surprising rate of patients foregoing first-line treatment 75
 
Highest rate of radiotherapy use in the US 75
 
Highest rate of patients foregoing therapy in the UK 75
 
CHAPTER 8 DRUG REGIMENS 77
 
Neoadjuvant drug regimens for resectable disease 77
 
Neoadjuvant drug regimens in combination with radiotherapy 77
 
Single-agent compounds see most use 78
 
Gemcitabine versus fluorouracil 79
 
Cisplatin as a radiosensitizer 79
 
No basis for gemcitabine and fluorouracil in combination 80
 
US favors single-agent fluorouracil 81
 
Single-agent gemcitabine drug of choice in Japan, Germany & Spain 81
 
Fluorouracil and cisplatin most popular in France 81
 
Deceptively high rate of gemcitabine and cisplatin in the UK 82
 
Neoadjuvant drug regimens without radiotherapy 82
 
Single-agent gemcitabine remains gold standard 84
 
High rates of drug therapy inexplicable due to lack of clinical trial data 84
 
Use of gemcitabine and cisplatin justified by Phase II trial data 84
 
Use of gemcitabine and oxaliplatin also unfounded 85
 
Single-agent gemcitabine drug of choice in Germany, UK, Japan and Spain 85
 
Nearly equal split between gemcitabine and fluorouracil use in the US 85
 
Gemcitabine and oxaliplatin unexpectedly popular in France 86
 
Gemcitabine and cisplatin use relatively high in the UK and Italy 86
 
Adjuvant drug regimens for resectable disease 87
 
Adjuvant drug regimens in combination with radiotherapy 87
 
Fluorouracil with radiotherapy is favorite choice 88
 
Gemcitabine shows potential as future replacement 89
 
Further lack of clinical trial data 89
 
Typically high rates of fluorouracil and cisplatin use in France 90
 
Adjuvant drug regimens without radiotherapy 90
 
Gemcitabine is favorite choice without radiotherapy 92
 
Use of fluorouracil is decreasing 92
 
Typically high rates of oxaliplatin use in France 92
 
Heavy use of gemcitabine and cisplatin in Italy 92
 
First-line drug regimens for non-resectable disease 93
 
First-line drug regimens in combination with radiotherapy 93
 
Gemcitabine and fluorouracil dominate first-line chemoradiation 94
 
Clinical trials support use of other regimens in the top five 95
 
Trend for cisplatin use in France continues 96
 
Highest use of single-agent capecitabine in the UK 96
 
First-line drug regimens without radiotherapy 97
 
Gemcitabine emerges as clear favorite 98
 
Fluorouracil to be completely sidelined? 99
 
Surprisingly low use of gemcitabine with oxaliplatin, considering benefits 99
 
Fluorouracil and gemcitabine do not display synergy 100
 
No clinical benefit from gemcitabine and cisplatin 101
 
Oxaliplatin is a close second in France 101
 
Unexplained high use of cisplatin in Italy 101
 
CHAPTER 9 CLINICAL TRIAL INVOLVEMENT 103
 
Neoadjuvant and/or adjuvant drug therapy 103
 
Low rates of trial involvement for resectable disease… 104
 
… with the UK as an exception 105
 
Use of unapproved drugs relatively low 105
 
Particularly low use of unapproved drugs in Germany, Italy, Spain and the UK 105
 
Highest use of unapproved agents in the US and France 106
 
First-line drug therapy 106
 
Only a quarter of non-resectable patients treated in clinical trials 108
 
Exceptionally low rates of trial involvement in Japan 108
 
Use of unapproved drugs relatively low 109
 
Particularly low use of unapproved drugs in the UK and Italy 109
 
Highest use of unapproved agents in France 109
 
CHAPTER 10 TREATMENT OUTCOMES 110
 
Resectable disease treatment outcomes 110
 
Survival following neoadjuvant and/or adjuvant therapy 110
 
Survival following no further cancer-directed therapy 112
 
Non-resectable disease treatment outcomes 114
 
Survival following first-line drug and radiotherapy 114
 
Survival following first-line drug therapy alone 116
 
Survival following first-line radiotherapy alone 117
 
Survival following no further cancer-directed therapy 119
 
CHAPTER 11 KEY PRESCRIBING INFLUENCES 121
 
Factors influencing physician prescription patterns 121
 
Neoadjuvant drug therapy 121
 
As expected, survival is of greatest importance… 123
 
…followed closely by quality of life 123
 
Aggressive nature of disease leaves some factors redundant 124
 
Lack of clinical trial data to prove benefits of combination with radiotherapy 124
 
Minor variations across the seven markets 124
 
Adjuvant drug therapy 124
 
Extended survival remains critical factor 126
 
Quality of life is a key factor following surgery 126
 
Surgery renders remaining factors irrelevant 127
 
Minor variations across the seven markets 127
 
First-line drug therapy 127
 
Where drug therapy is never curative, improved quality of life dominates 128
 
Survival is only of secondary importance 129
 
Halting disease progression linked to improved quality of life 129
 
Dire prognosis leaves some factors redundant 129
 
Minor variations across the seven markets 130
 
Performance of key cytotoxics 130
 
Key cytotoxics within specific lines of therapy 132
 
Neoadjuvant drug therapy 133
 
Adjuvant drug therapy 134
 
First-line drug therapy 136
 
CHAPTER 12 PIPELINE OVERVIEW 138
 
Unmet needs 138
 
Current late-phase pipeline overview 138
 
Insegia (G17DT) 140
 
Orathecin (rubitecan) 141
 
Eloxatin (oxaliplatin) 142
 
Alimta (pemetrexed) 143
 
Erbitux (cetuximab) 144
 
Tarceva (erlotinib) 145
 
Avastin (bevacizumab) 146
 
Virulizin 147
 
CHAPTER 13 POPULATION DATA 149
 
US 149
 
Japan 153
 
France 157
 
Germany 161
 
Italy 165
 
Spain 169
 
UK 173
 
CHAPTER 14 KEY PRESCRIBING INFLUENCES DATA 177
 
Gemcitabine 177
 
Fluorouracil 179
 
Cisplatin 181
 
APPENDIX A 183
 
Bibliography 183
 
List of tables 190
 
List of figures 197
 
List of figures 197
 
APPENDIX B 201
 
Physician research methodology 201
 
Physician sample breakdown 201
 
US 201
 
Japan 202
 
France 202
 
Germany 203
 
Italy 203
 
Spain 204
 
UK 204
 
Contributing experts 205
 
Key opinion leader interview transcripts 206
 
Doctor Antoine Adenis, Department of Digestive and Urological Cancer, Centre Oscar Lambert, Lille, France 206
 
Doctor A. William Blackstock Jr, Associate Professor of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA 216
 
Professor John Neoptolemos, Professor & Head of Department, Department of Surgery, University of Liverpool, Liverpool, UK 230
 
APPENDIX C 241
 
The survey questionnaire 241
 
1. Diagnosing pancreatic cancer 241
 
2. Resectable patients 244
 
3. Non-resectable patients 251
 
4. Key prescribing influences 256
 
Disclaimer 259