Stakeholder Insight: Renal Cancer - Targeted therapies rapidly take hold of market

ABOUT DATAMONITOR HEALTHCARE 2
About the Oncology pharmaceutical analysis team 2
Andrew Paramore - Oncology Lead Analyst & Head of Product Development 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the Renal Cancer market 4
Related reports 5
Upcoming reports 5
CHAPTER 2 INTRODUCTION AND SCOPE 7
Coverage of the Stakeholder Insight survey 7
Disease definition and epidemiology 7
Segmentation of the renal cancer population 7
Current drug treatment practice for renal cancer 7
Key unmet needs within the renal cancer market 7
Potential of pipeline drugs for renal cancer 8
CHAPTER 3 COUNTRY TREATMENT TREES 9
Introduction 9
US 11
Japan 13
France 15
Germany 17
Italy 19
Spain 21
UK 23
CHAPTER 4 DISEASE OVERVIEW, EPIDEMIOLOGY AND PATIENT SEGMENTATION 25
Disease definition 25
TNM is most commonly used staging system for RCC 26
Etiology 28
Obesity accounts for 30% of RCC incidences 28
Smoking accounts for 20% of RCC incidences 28
Hypertension influences RCC risk 28
Family history of RCC associated with an increased risk for RCC 28
No conclusive evidence over occupational risk factors 29
Disease incidence 29
RCC incidence rates vary considerably across the seven major markets; RCC is more prevalent in males 29
RCC incidence rate increasing steadily 30
Incidence of RCC across seven major markets will total 86,800 in 2007 30
CHAPTER 5 DIAGNOSIS AND PRESENTATION IN RCC 33
Disease subtype at presentation 33
Renal cell carcinoma accounts for the majority of kidney cancer diagnoses across the seven major markets 33
Distribution of kidney cancer subtypes does not vary significantly across the seven major markets 34
Disease stage at presentation 36
High proportion of RCC patients treated by medical oncologists present with Stage IV disease 37
Higher apparent proportion of Stage IV RCC patients at diagnosis in Germany may reflect difference in referral patterns 38
Urologists rather than medical oncologists primarily responsible for RCC management in Japan; explains apparently higher proportion of early-stage disease in Japan 38
Uncertain whether screening program would significantly increase proportion of RCC diagnosed at early stage 39
CHAPTER 6 TREATMENT OPTIONS FOR RCC 40
Overview of treatment options in RCC 40
Overview of pharmacological therapies in RCC: targeted therapy approvals provide much-needed therapeutic option in RCC 40
Overview of surgery in RCC: surgery is principal treatment option for Stage I-III RCC 43
Trends in surgery and drug therapy in RCC across the seven major markets 45
High percentage of Stage I-III RCC patients receive surgery across all seven major markets 45
Adjuvant therapy in Stage I-III patients limited to clinical trials 47
Small proportion of non-surgically treated patients treated with drug therapy 51
Majority of Stage IV patients receive drug therapy 52
CHAPTER 7 TREATMENT TRENDS: FIRST-LINE DRUG REGIMENS FOR STAGE IV RCC 55
First-line prescribing trends in Stage IV RCC by class of drug therapy 55
Use of targeted therapies across seven major markets for Stage IV RCC reflects country-specific market dynamics 55
US: targeted therapies have already captured a large share of the market 56
Japan: cytokine therapy dominates RCC market in absence of approved targeted therapies 56
France: use of targeted therapies for RCC is highest compared to other major European healthcare markets 57
Italy and UK: cost-containment measures limit uptake of targeted therapies for RCC 57
Use of cytotoxic therapy in the first-line is highest in Germany 58
First-line prescribing trends in Stage IV RCC by specific drug or regimen 59
Sutent versus Nexavar: Sutent is most commonly prescribed first-line targeted therapy for RCC 67
Interferon alfa versus interleukin: interferon alfa is the most commonly prescribed cytokine therapy for first-line treatment of RCC 69
Avastin used off-label in the US for Stage IV RCC; likely to capture more of first-line market 71
Torisel may experience modest uptake for low performance status RCC patients 72
CHAPTER 8 TREATMENT TRENDS: SECOND-LINE AND THIRD-LINE DRUG REGIMENS IN RCC 74
Recurrence patterns and second-line treatment in RCC 74
Recurrence rates increase with disease stage at diagnosis 74
High proportion of Stage III and Stage IV RCC patients progress to receive a second-line drug regimen 77
Second-line prescribing trends in RCC by class of drug therapy 83
Targeted therapies are predominant class of second-line drug therapy for RCC 83
Second-line prescribing trends in RCC by specific drug or regimen 85
Nexavar and Sutent are the predominant drug therapies in second-line RCC treatment 96
Nexavar is preferred second-line therapy for Sutent-refractory patients 96
Nexavar marginally preferred over Sutent as second-line therapy in patients treated with interferon alfa or interleukin-2 as first-line therapy 97
Second-line use of interleukin-2 mainly accounted for by Japanese RCC patients 98
Avastin third most prescribed second-line drug in US, France, Germany and Spain 98
Gemzar is third most popular second-line therapy in Italy 99
Torisel likely to capture a share of second-line market in RCC 99
Third-line prescribing trends in RCC 99
Less than a third of second-line RCC patients progress to a third-line regimen 99
Third-line prescribing trends by specific drug or regimen 101
Avastin most prescribed third-line RCC therapy across the seven major markets 109
5-fluorouracil is favored third-line drug in Japan 110
CHAPTER 9 PRESCRIBING INFLUENCES AND BRAND ASSESSMENT FOR RCC DRUG THERAPIES 111
Factors influencing prescribing decisions in RCC 111
Efficacy is the major prescribing influence in RCC 112
Toxicity also an important prescribing influence 113
Cost issues possibly not as important as for other indications 113
Other factors exert minor influence on RCC treatment decisions 113
Physician perception of existing therapies in RCC 114
Efficacy considered to be greatest for Sutent 115
Toxicity profiles most favorable for Sutent, Nexavar and Avastin 117
Cost: interferon alfa considered best in terms of cost issues 119
Convenience of administration highest for Sutent and Nexavar due to oral availability 122
Patient preference reflects toxicity profile 122
Physician familiarity highest for interleukin-2 and interferon alfa 122
Brand map overview of attributes and drug perception in RCC 122
Interpreting a brand map 122
CHAPTER 10 TREATMENT OUTCOMES AND UNMET NEEDS IN RCC 125
Treatment outcomes 125
Remission rates 125
Remission duration 126
Unmet needs in renal cancer 128
Efficacious drugs for metastatic disease is greatest unmet need in RCC 129
Improving treatment outcomes in RCC 130
Drug combinations likely to become more common in RCC 130
Sutent and Nexavar being investigated in adjuvant setting 130
CHAPTER 11 RCC LATE-PHASE PIPELINE OVERVIEW 132
Desired attributes of pipeline drugs in RCC 132
Products in Phase III development for RCC 134
RCC Phase III pipeline overview 134
Oncophage (vitespen), Antigenics 135
Reniale, LipoNova 136
TroVax (MVA 5T4), Oxford Biomedica/Sanofi Aventis 137
Avastin (bevacizumab), Genentech/Roche 138
Certican (everolimus), Novartis 139
Rencarex (WX-G250), Wilex 140
Tykerb (lapatinib), GlaxoSmithKline 141
Pazopanib, GlaxoSmithKline 142
BIBLIOGRAPHY 144
Journals 144
Websites 150
Other 152
APPENDIX A 154
Physician research methodology 154
Physician sample breakdown 154
US 154
Japan 155
France 155
Germany 156
Italy 156
Spain 157
UK 157
Contributing experts 158
APPENDIX B 159
The survey questionnaire 159
Section 2 - Treatment 165
Section 3 - Product Profiles 176
Section 4 - Pipeline Products 178
The opinion leader discussion guide 180
Referral and treatment in RCC 180
First-line drug therapy in RCC 181
Second-line drug therapy in RCC 181
Unmet needs, pipeline drugs and future treatments 182
Disclaimer 183
List of Tables
Table 1: TNM staging of RCC and associated 5-year survival rates 27
Table 2: Incidence rates of kidney cancer across the seven major markets, 2002 29
Table 3: Estimated RCC incidence across the seven major markets, 2007-17 31
Table 4: Breakdown of renal cancer subtypes at presentation for each of the seven major markets (%), 2007 35
Table 5: Percentage of RCC patients presenting with each stage of disease at first diagnosis in the seven major markets (%), 2007 36
Table 6: Summary of RCC drug regimens, July 2007 41
Table 7: Unapproved drug therapies for RCC used by physicians responding to Datamonitor renal cancer survey, 2007 43
Table 8: Principal surgical options for the treatment of RCC, 2007 44
Table 9: Percentage of Stage I-III RCC patients receiving surgery/not receiving surgery averaged across the seven major markets, 2007 45
Table 10: Percentage of Stage I RCC patients undergoing surgery who also receive adjuvant and/or neoadjuvant drug therapy in the seven major markets, 2007 48
Table 11: Percentage of Stage II RCC patients undergoing surgery who also receive adjuvant and/or neoadjuvant drug therapy in the seven major markets, 2007 49
Table 12: Percentage of Stage III RCC patients undergoing surgery who also receive adjuvant and/or neoadjuvant drug therapy in the seven major markets, 2007 50
Table 13: Percentage of non-surgically treated Stage I-III RCC patients receiving drug therapy in the seven major markets, 2007 51
Table 14: Percentage of Stage IV RCC patients receiving drug therapy in the seven major markets, 2007 53
Table 15: Percentage of Stage IV RCC patients who undergo first-line systemic therapy with each drug class in the seven major markets, 2007 55
Table 16: Percentage of Stage IV RCC patients who undergo first-line systemic therapy receiving each drug or regimen, in the seven major markets, 2007 60
Table 17: Percentage of RCC patients relapsing at each stage averaged over the seven major markets, 2007 74
Table 18: Disease stage at relapse for RCC patients who initially present with Stage I-III RCC averaged across the seven major markets (%), 2007 76
Table 19: Percentage of RCC patients initially treated with drug therapy who progress/do not progress to a second-line drug regimen averaged across the seven major markets, 2007 78
Table 20: Percentage of Stage III RCC patients initially treated with drug therapy who progress/do not progress to receive a second-line drug regimen in each of the seven major markets, 2007 80
Table 21: Percentage of Stage IV RCC patients initially treated with drug therapy who progress/do not progress to receive a second-line drug regimen in each of the seven major markets, 2007 82
Table 22: Percentage of RCC patients who receive second-line drug treatment with each class of drug, averaged across the seven major markets, 2007 84
Table 23: Percentage of RCC patients who undergo second-line drug therapy receiving each drug or regimen as a second-line treatment, in the seven major markets, 2007 86
Table 24: Percentage of patients who receive each drug as second-line therapy according to treatment initially received, averaged across the seven major markets, 2007 94
Table 25: Comparison of clinical trial data for Sutent and Nexavar in cytokine-refractory patients, 2007 98
Table 26: Percentage of second-line RCC patients progressing to third-line regimen in the seven major markets, 2007 100
Table 27: Percentage of RCC patients who undergo third-line drug therapy receiving each drug or regimen, in the seven major markets, 2007 102
Table 28: Relative weighting given to each prescribing influence for RCC drug therapy across the seven major markets, 2007 111
Table 29: Mean rating (weighted by importance of attribute) given by physicians to currently approved drugs in RCC, 2007 114
Table 30: Comparison of Phase III trial data for Sutent, Nexavar and Torisel in RCC 116
Table 31: Summary of selected clinical trials of interferon alfa and interleukin-2 117
Table 32: Toxicity profile comparison: most commonly reported Grade 3 or 4 adverse events in large-scale clinical trials of RCC drugs, 2007 119
Table 33: Comparison of estimated costs for drug treatments in RCC, 2007 121
Table 34: Mean percentage of RCC patients achieving remission by disease stage in the seven major markets, 2007 125
Table 35: Mean duration of remission (in months) for RCC patients achieving remission before relapsing in the seven major markets, 2007 127
Table 36: Ongoing Phase III trials of targeted therapies as adjuvant treatment following surgery in RCC, July 2007 131
Table 37: Drugs in Phase III development for RCC, August 2007 135
Table 38: US physician sample breakdown, 2007 154
Table 39: Japan physician sample breakdown, 2007 155
Table 40: France physician sample breakdown, 2007 155
Table 41: Germany physician sample breakdown, 2007 156
Table 42: Italy physician sample breakdown, 2007 156
Table 43: Spain physician sample breakdown, 2007 157
Table 44: UK physician sample breakdown, 2007 157
List of Figures
Figure 1: Population, treatment and treatment outcome data for RCC in the US, 2007 11
Figure 2: Population, treatment and treatment outcome data for RCC in US, 2007 (continued) 12
Figure 3: Population, treatment and treatment outcome data for RCC in Japan, 2007 13
Figure 4: Population, treatment and treatment outcome data for RCC in Japan, 2007 (continued) 14
Figure 5: Population, treatment and treatment outcome data for RCC in France, 2007 15
Figure 6: Population, treatment and treatment outcome data for RCC in France, 2007 (continued) 16
Figure 7: Population, treatment and treatment outcome data for RCC in Germany, 2007 17
Figure 8: Population, treatment and treatment outcome data for RCC in Germany, 2007 (continued) 18
Figure 9: Population, treatment and treatment outcome data for RCC in Italy, 2007 19
Figure 10: Population, treatment and treatment outcome data for RCC in Italy, 2007 (continued) 20
Figure 11: Population, treatment and treatment outcome data for RCC in Spain, 2007 21
Figure 12: Population, treatment and treatment outcome data for RCC in Spain, 2007 (continued) 22
Figure 13: Population, treatment and treatment outcome data for RCC in the UK, 2007 23
Figure 14: Population, treatment and treatment outcome data for RCC in the UK, 2007 (continued) 24
Figure 15: Relative prevalence of RCC subtypes, 2005 26
Figure 16: Estimated RCC incidence across the seven major markets, 2007-17 32
Figure 17: Breakdown of kidney cancer subtype at diagnosis averaged over the seven major markets, 2007 34
Figure 18: Breakdown of renal cancer subtypes at presentation for each of the seven major markets (%), 2007 35
Figure 19: Percentage of RCC patients presenting with each stage of disease at first diagnosis in the seven major markets, 2007 37
Figure 20: Timeline of recent approvals of targeted therapies for metastatic RCC, December 2005-May 2007 42
Figure 21: Percentage of Stage I-III RCC patients receiving surgery/not receiving surgery averaged across the seven major markets, 2007 46
Figure 22: Percentage of Stage I-III RCC patients not receiving surgery in each country across the seven major markets, 2007 47
Figure 23: Percentage of non-surgically treated Stage I-III RCC patients who receive drug therapy, seven major markets, 2007 52
Figure 24: Percentage of Stage IV RCC patients receiving drug therapy, in the seven major markets, 2007 54
Figure 25: Percentage of Stage IV RCC patients who undergo first-line systemic therapy with each drug class, in the seven major markets, 2007 56
Figure 26: Top three first-line drug therapies for Stage IV RCC, US, 2007 61
Figure 27: Top three first-line drug therapies for Stage IV RCC, Japan, 2007 62
Figure 28: Top three first-line drug therapies for Stage IV RCC, France, 2007 63
Figure 29: Top three first-line drug therapies for Stage IV RCC, Germany, 2007 64
Figure 30: Top three first-line drug therapies for Stage IV RCC, Italy, 2007 65
Figure 31: Top three first-line drug therapies for Stage IV RCC, Spain, 2007 66
Figure 32: Top three first-line drug therapies for Stage IV RCC, UK, 2007 67
Figure 33: Percentage of RCC patients relapsing at each stage averaged over the seven major markets, 2007 75
Figure 34: Disease stage at relapse for RCC patients who initially present with Stage I-III RCC averaged across the seven major markets (%), 2007 77
Figure 35: Percentage of RCC patients initially treated with drug therapy who progress/do not progress to a second-line drug regimen averaged across the seven major markets, 2007 79
Figure 36: Percentage of Stage III RCC patients initially treated with drug therapy who progress/do not progress to receive a second-line drug regimen in each of the seven major markets, 2007 81
Figure 37: Percentage of Stage IV RCC patients initially treated with drug therapy who progress/do not progress to receive a second-line drug regimen in each of the seven major markets, 2007 83
Figure 38: Proportion of RCC patients who receive second-line drug treatment with each class of drug at second-line, averaged across the seven major markets, 2007 85
Figure 39: Top three second-line drug therapies for RCC, US, 2007 87
Figure 40: Top three second-line drug therapies for RCC, Japan, 2007 88
Figure 41: Top three second-line drug therapies for RCC, France, 2007 89
Figure 42: Top three second-line drug therapies for RCC, Germany, 2007 90
Figure 43: Top three second-line drug therapies for RCC, Italy, 2007 91
Figure 44: Top three second-line drug therapies for RCC, Spain, 2007 92
Figure 45: Top three second-line drug therapies for RCC, UK, 2007 93
Figure 46: Correlation between first-line drug regimen and choice of second-line drug regimen in RCC, averaged across the seven major markets, 2007 95
Figure 47: Percentage of second-line RCC patients progressing to third-line regimen in the seven major markets, 2007 100
Figure 48: Top three third-line drug therapies for RCC, US, 2007 103
Figure 49: Top three third-line drug therapies for RCC, Japan, 2007 104
Figure 50: Top three third-line drug therapies for RCC, France, 2007 105
Figure 51: Top three third-line drug therapies for RCC, Germany, 2007 106
Figure 52: Top three third-line drug therapies for RCC, Italy, 2007 107
Figure 53: Top three third-line drug therapies for RCC, Spain, 2007 108
Figure 54: Top three third-line drug therapies for RCC, UK, 2007 109
Figure 55: Relative weighting given to each prescribing influence for RCC drug therapy across the seven major markets, 2007 112
Figure 56: Mean rating (weighted by importance of attribute) given by physicians to existing RCC drugs, 2007 115
Figure 57: Overview brand map of attributes versus brand perception in RCC, 2007 124
Figure 58: Mean percentage of RCC patients achieving remission by disease stage across the seven major markets, 2007 126
Figure 59: Mean duration of remission (in months) for RCC patients achieving remission before relapsing in the seven major markets, 2007 128
Figure 60: Mean physician ratings of unmet needs in renal cancer, 2007 129
Figure 61: Order of importance of desired clinical attributes for pipeline drugs in metastatic RCC, 2007 132
Figure 62: Clinical targets necessary to convince physicians to use pipeline drug instead of Sutent in first-line for RCC, 2007 133
Figure 63: Clinical targets necessary to convince physicians to use pipeline drug in cytokine-refractory patients in RCC, 2007 134