Contents:

About Us HEALTHCARE 2 About the Oncology pharmaceutical analysis team 2 Chapter 1. Executive summary 3 Scope of the analysis 3 Ourinsight into the NSCLC market 4 Chapter 2. Introduction and scope 19 Coverage of the Stakeholder Insight Survey 19 Disease definition & epidemiology 19 Diagnosis 19 Resectable disease 19 Non-resectable disease 19 Drug regimens 20 Unmet needs 20 Future focus 20 Chapter 3. Country treatment trees 22 US 23 Japan 25 France 27 Germany 29 Italy 31 Spain 33 UK 35 Chapter 4. Disease definition and epidemiology 37 Lung cancer is divided into two major subtypes according to its biology, therapy and prognosis 37 Non-small cell lung cancer accounts for more than 75% of all lung cancers 38 Three major histological subtypes of NSCLC exist 38 Squamous cell carcinoma is associated with relatively better prognosis than other histological subtypes 38 Adenocarcinoma: the most prevalent form of NSCLC today 38 Bronchioalveolar carcinoma is a distinct subclass of adenocarcinoma 39 Large cell carcinoma is often advanced at the time of diagnosis 39 Epidemiology of NSCLC 40 The NSCLC death rate now exceeds that of breast, prostate and colon cancers combined 40 Chapter 5. Segmenting the nsclc population 44 Segmentation of NSCLC is usually based on the AJCCs TNM staging system 44 Over half of all NSCLC patients across the seven major markets are diagnosed in the advanced stages 46 The majority of NSCLC patients are diagnosed in stage IIIB or above 48 Earlier diagnosis of NSCLC in Japan? 48 Extent of resection across the seven major markets 48 Surgical resection offers a cure but the greatest benefit is restricted to early-stage NSCLC 49 Resectable versus non-resectable disease 49 The general trend across the major markets shows that suitability for curative surgery diminshes as disease stage advances 49 Low surgery rate in the UK in early stages 51 Is there overuse of surgery within Japan? 53 The trend of low surgical resection within the UK is repeated at stage IIIA 53 More aggressive surgical rates for advanced stage NSCLC in Germany 55 Chapter 6. Treatment of resectable disease 59 The use of drug therapy in combination with surgery 59 Data from Phase III neo-adjuvant clinical trials is limited 59 The majority of NSCLC neo-adjuvant studies involve stage IIIA patients 59 The largest neo-adjuvant trial in early stage NSCLC to date was halted 62 Increased post-operative complications call into question the use of neo-adjuvant chemotherapy 63 Adjuvant therapy historically showed negative results and was associated with stigma... 65 ...until the International Adjuvant Lung Cancer Trial (IALT) demonstrated improved five-year survival 65 Three key early-stage NSCLC adjuvant chemotherapy studies support the IALT trial 66 Combination of neo-adjuvant and adjuvant chemotherapy show favorable results 69 Chemotherapy approaches vary across the four major stages of NSCLC 70 Physicians prefer to use combined neo-adjuvant and adjuvant chemotherapy across the seven major markets for stage I/II resectable patients... 71 Physicians prescribe similar percentages of adjuvant and neo-adjuvant treatments for stage I/II patients 73 Low drug useage for stage I/II resectable patients in Italy... 73 ...while drug use is greater in the UK 74 Minimal differences are found in the prescribing of neo-adjuvant and adjuvant chemotherapy between stages IIIA and IIIB... 74 ...except in France and the UK 75 Both France and the UK shift to more aggressive use of combined neo-adjuvant and adjuvant treatment in stage IIIB NSCLC 76 The combined use of neo-adjuvant and adjuvant therapy is the preferred treatment modality for stage III NSCLC... 77 Combined neo-adjuvant and adjuvant treatment is prescribed most frequently for resectable stage IV NSCLC 77 Combined neo-adjuvant and adjuvant treatment is prescribed for the majority of stage IV resectable NSCLC across the seven major markets... 78 ...except in Japan 78 Chemotherapy approaches by disease stage 79 With advancing stage of disease physicians switch from adjuvant chemotherpay alone to combined neo-adjuvant and adjuvant approaches 80 The use of drug therapy is reduced in patients with advanced disease 81 Chapter 7. Treatment of non-resectable disease 82 Increasing use of chemotherapy with advancing disease in non-resectable NSCLC 83 Early stage non-resectable patients are ideal candidates for radiotherapy 83 Elderly, frail patients of poor performance status comprise a small cohort of early-stage NSCLC patients who do not receive drug treatment 84 Performance status is deemed the key factor to chemotherapy prescribing within advanced non-resectable patients 84 There is high unmet need for drugs that can be administered to poor perfomance NSCLC patients 85 Phase III trials demonstrate greater response to Cell Therapeutics Xyotax among advanced, pre-menopausal, poor performance status females 86 Quality of life becomes increasingly important within the last few months of a NSCLC patients life 87 Use of chemotherapy treatment for non-resectable patients shows little variation at market level 88 US and German physicians take an aggressive approach to chemotherapy treatment of non-resectable stage IV patients 89 Japanese physicians are the lowest prescribers of chemotherapy treatment 90 Chapter 8. Current drug regimens 91 Current first-line NSCLC drug regimens 92 Single, doublet and triplet chemotherapy regimens by disease stage 92 Doublet-regimens dominate the first-line treatment of NSCLC 92 Single, doublet and triplet chemotherapy regimens by market 96 Doublet regimens dominate the first-line treatment of stage IV disease in all seven major markets 96 Platinum-based regimens by disease stage 98 Carboplatin-based regimens lead the first-line treatment of NSCLC 98 Non-platinum-based regimens are suitable for patients who are unable to tolerate the toxicities of platinum regimens 102 The prescribing of oxaliplatin-based therapies is minimal 104 Platinum-based regimens by market 104 Carboplatin-based regimens dominate the treatment of stage IV NSCLC across the seven major markets... 105 ...except in Italy 106 Use of platinum-taxane doublets versus platinum-non-taxane third-generation cytotoxic doublet regimens by disease stage 107 Platinum-taxane versus platinum-non-taxane cytotoxic doublet regimens by market 110 Platinum-non-taxane third-generation cytotoxic regimens dominate the treatment of stage IV disease across all seven major markets 110 The top three first-line NSCLC drug regimens by disease stage 111 Carboplatin-paclitaxel is the leading drug-regimen in first-line NSCLC 113 The top three first-line drug regimens by market 113 Carboplatin-paclitaxel is still at the forefront of first-line stage IV treatment, but only within three markets 113 In France and Italy the first-line stage IV drug regimen of choice is platinum-gemcitabine 116 UK-based physicians reflect new emphasis 116 Japanese physicians pefer carboplatin-etoposide 117 More market variance is seen in the top three first-line drug regimens at stage IV than at stage I/II NSCLC 118 Single-agent regimens by disease stage 118 Molecular targeted therapeutics versus cytotoxics by disease stage 121 Molecular targeted therapeutics versus cytotoxics by market 123 US physicians have the greatest use of targeted therapy-based regimens for first-line advanced NSCLC 123 Iressa-, Tarceva-, Avastin- and Erbitux-based regimens by disease stage 124 First-line use of Iressa-, Tarceva-, Avastin- and Erbitux-based regimens by market 128 Avastin-based regimens are the leading choice for first-line advanced NSCLC, within the US, UK, France and Italy 129 Iressa is the most popular targeted therapeutic in Japan 129 Current second-line NSCLC drug regimens 130 The leading second-line NSCLC drug regimens currently used by physicians across the seven major markets 130 Carboplatin-paclitaxel dominates the second-line treatment of NSCLC across the seven major markets 132 Carboplatin-gemcitabine proves a popular choice among Japanese physicians... 134 ...whereas Italian physicians prefer approved single-agent docetaxel 134 Current third-line NSCLC drug regimens 134 The leading third-line NSCLC drug regimens currently used by physicians across the seven major markets 134 Carboplatin-paclitaxel is the leading third-line regimen across the seven major markets... 136 Platinum-triplet regimens are the leading third-line treatment in the US 137 AstraZenecas Iressa (gefitinib) is reported as the leading third-line regimen among Italian physicians 137 Current NSCLC drug regimens by line setting 137 Platinum-based regimens by line setting 137 Excision repair cross-complementation group 1 (ERCC1) emerges as a marker for cisplatin-resistance 140 Molecular targeted therapeutics versus cytotoxic therapy by line setting 141 As NSCLC patients progress from the first- to the third-line setting, the use of targeted therapeutics doubles 142 Iressa-, Tarceva-, Avastin- and Erbitux-based regimens by line setting 143 The impact of Alimta and Tarceva on current Taxotere prescribing 145 First-line prescribing of Taxotere-platinum doublet has reached a plateau 147 Taxotere is associated with hematological toxicities 147 Physicians now switching to Alimta due to improvement upon Taxoteres toxicity profile 148 Despite costing twice as much as Taxotere, Alimta is considered cost-effective 149 Alimta may prove a modest challenge to Taxotere in the first-line setting of NSCLC 150 Tarcevas ability to improve progression-free surival renders the agent a significant threat to Alimta and Taxotere in the second-line setting of NSCLC 151 NSCLC physicians may favor Tarcevas favourable toxicity profile to those of Taxotere and Alimta 152 Tarcevas superior toxicity profile is ideal for PS2 patients who cannot tolerate chemotherapy 154 Chapter 9. Unmet needs 156 Physician rating of clinical unmet needs within the NSCLC market 156 Unmet needs within todays NSCLC market 157 With just 15% of NSCLC patients surviving beyond five years, effective agents that improve survival are needed 157 Earlier diagnosis of NSCLC could improve patient prognosis 158 Virtually all NSCLC patients relapse following first-line chemotherapy 158 Opportunity for a first-line agent with reduced toxicity 159 Cost-effective molecular targeted therapies are required 160 Despite constituting about 65% of all NSCLC patients, suitable therapeutics for the elderly remain elusive 161 BAC and adenocarcinoma patients are underserved 163 Tarceva and Iressas secondary resistance is linked with mutations 163 Optimal patient selection is vital for successful development of targeted therapies 164 Analysis of NSCLC unmet needs by country 164 Agents to improve metastatic survival is the greatest unmet need across all seven major markets... 166 ...expect in Japan 166 An improved patient selection process is the least important unmet need across the seven major markets 166 High unmet need for Effective therapeutics for elderly patients in Japan 166 Chapter 10. Potential of emerging therapies 168 Overview of the key NSCLC candidates 170 Genentech/Roches Avastin (bevacizumab) is the first anti-angiogenic agent to gain approval 170 Avastins first-line Phase III trial demonstrates 61% improvement of progression-free survival 172 Erbitux (cetuximab), the EGFR monoclonal antibody, is involved in numerous ongoing NSCLC trials 173 Nexavar (sorafenib) is the first oral multi-tyrosine kinase inhibitor to reach the market 175 AstraZenecas Zactima (vandetanib ZD6474) targets both VEGF and EGFR 176 Amgens Vectibix (panitumumab) is a fully humanized monoclonal antibody targeting first- and-second-line NSCLC 177 Phase II Vectibix data show outstanding toxicity profile 178 Physician ratings of key pipeline NSCLC candidates 178 Physician ratings of the five NSCLC candidates are similar suggesting companies need to differentiate their products 178 Physician ratings of key pipeline NSCLC candidates by country analysis 180 Surveyed physicians are more aware of Avastin and Erbitux than Nexavar, Zactima and Vectibix across the seven major markets 181 Avastin is preferred by UK, Spanish and French physicians... 181 Nexavar is preferred to Zactima within the UK and US 182 French physician physicians favor Zactima over Nexavar 183 Vectibix could compete well with Erbitux 183 Chapter 11. Future focus 184 Perceived future drug regimen prescribing 184 Platinum-doublet regimens will continue to form the backbone of NSCLC treatment 186 Companies involved in the NSCLC arena must differentiate their products 187 Immunotherapies are poorly perceived by physicians 188 Although doublet cytotoxics will remain at the forefront of future treatment of NSCLC, Avastin and Erbitux may reduce the use of platinum-triplet regimens 189 Influences on physician prescribing within the future NSCLC market 190 First-line combination chemotherapy is considered the most important scenario within the future NSCLC market 192 Avastins recent toxicity concerns do not seem to have affected physicians perceptions of the agent... 193 ...except within Japan 195 APPENDIX A 196 Supplementary data 196 First-line stage I/II drug regimens 196 First-line stage IIIA drug regimens 198 First-line stage IIIB drug regimens 199 First-line stage IV drug regimens 200 Second-line drug regimens 201 Third-line drug regimens 202 APPENDIX B 203 Bibliography List of Tables List of Figures 220 Physician research methodology 224 Contributing experts 224 Key opinion leader transcripts 224 APPENDIX C 225 The survey questionnaire 225 1.0 Segmenting the patient population 225 Segmenting patients by suitability for neo-adjuvant and/or adjuvant therapy 225 Segmenting patients by suitability for drug therapy 226 2.0 Current drug treatment practice 227 3.0 Unmet needs 233 4.0 Future drug useage 233 Disclaimer List of Tables Table 1: NSCLC physician breakdown surveyed by We, 2006 4 Table 2: Crude incidence rates of lung cancer by gender (per 100,000) in the seven major markets, 2002 41 Table 3: Forecast incidence of lung cancer (types C33 and C34) in the seven major markets, 2002-2016 41 Table 4: Forecast incidence of NSCLC in the seven major markets, 2002-2016 43 Table 5: American Joint Committee on Cancer TNM staging of NSCLC 45 Table 6: American Joint Committee on Cancer TNM staging of NSCLC 46 Table 7: NSCLC patients diagnosed at each stage (I-IV) (%), 2006 47 Table 8: Mean NSCLC patients suitable for surgery with curative intent, across the seven major markets, (%) 2006, 50 Table 9: Stage I/II NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 52 Table 10: Stage IIIA NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 54 Table 11: Stage IIIB NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 55 Table 12: Stage IV NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 56 Table 13: Summary results of Martini et al. (1993) Phase III neo-adjuvant trial in stage IIIA NSCLC patients 60 Table 14: Summary results of Roth et al. (1994) and Rossell et al. (1994) Phase III neo-adjuvant trials in stage IIIA NSCLC patients 61 Table 15: Preliminary results of Pisters et al. (2005) Phase III neo-adjuvant trial in stage I-IIIA NSCLC patients 62 Table 16: Summary of Sorensen et al. (2005) Phase III neo-adjuvant trial in stage I-IIIA NSCLC patients 63 Table 17: Arguments for and against neo-adjuvant NSCLC chemotherapy 64 Table 18: Summary of results of the International Adjuvant Lung Cancer Trial (IALT) 66 Table 19: Summary of key Phase III adjuvant NSCLC trials CALC GB 9633 NCIC CTG JBR.10 and ANITA 67 Table 20: Arguments for and against adjuvant NSCLC chemotherapy 68 Table 21: Arguments for and against combined neo-adjuvant and adjuvant chemotherapy 70 Table 22: Chemotherapy approaches for resectable stage I/II NSCLC patients in the seven major markets (%), 2006 71 Table 23: Chemotherapy approaches for resectable stage IIIA NSCLC patients across the seven major markets (%), 2006 75 Table 24: Chemotherapy approaches for resectable stage IIIB NSCLC patients in the seven major markets (%), 2006 75 Table 25: Chemotherapy approaches for resectable stage IV NSCLC patients in the seven major markets (%), 2006 77 Table 26: Mean chemotherapy approaches for resectable NSCLC patients between stages I and IV, across the seven major markets (%), 2006 79 Table 27: Mean use of chemotherapy treatment within non-surgical NSCLC patients between stage I/II and stage IV, across the seven major markets (%), 2006 82 Table 28: Use of chemotherapy treatment in non-resectable NSCLC patients by stage across the seven major markets (%), 2006 88 Table 29: Use of first-line single, doublet and triplet chemotherapy regimens for stage I/II-IV NSCLC across the seven major markets (%), 2006 93 Table 30: Use of first-line platinum-based regimens for stage I/II and stage IIIA NSCLC in the seven major markets (%), 2006 99 Table 31: Use of first-line platinum-based regimens for stage IIIB to stage IV across the seven major markets (%), 2005 100 Table 32: Arguments for platinum-based versus non-platinum-based regimens in NSCLC 103 Table 33: Use of first-line platinum-taxane versus platinum-non-taxane third-generation cytotoxic regimens for the treatment of stage I/II-IV NSCLC in the seven major markets (%), 2006 108 Table 34: Use of the top-three first-line drug regimens for the treatment of stage I/II-IV NSCLC in the seven major markets (%), 2006 111 Table 35: Use of first-line single-agent regimens for the treatment of stage I/II-IV NSCLC across the seven major markets (%), 2006 119 Table 36: Use of first-line MTT-based regimens and cytotoxics for stage I/II-IV NSCLC in the seven major markets (%), 2006 122 Table 37: Percentage use of first-line Iressa-, Tarceva-, Avastin- and Erbitux-based regimens for the treatment of stage I/II-IV NSCLC in the seven major markets (%), 2006 125 Table 38: Use of the top three second-line drug regimens for the treatment of all stages of NSCLC in the seven major markets (%), 2006 130 Table 39: Use of the top three third-line drug regimens for the treatment of all stages of NSCLC in the seven major markets (%), 2006 134 Table 40: Mean use of platinum-based and non-platinum-based regimens for the treatment of all stages of NSCLC by line setting, across the seven major markets, (%), 2006 138 Table 41: Mean use of molecular targeted therapeutics versus cytotoxic therapy for the treatment of all stages of NSCLC, within the three line settings, across the seven major markets, (%) 2006 141 Table 42: Mean use of gefitinib, erlotinib, bevacizumab and cetuximab-based regimens for the treatment of all stages of NSCLC, within the three line settings, across the seven major markets (%), 2006 143 Table 43: Mean use of Taxotere, Alimta and Tarceva within NSCLC, across the seven major markets (%), 2006 147 Table 44: TAX-317 and TAX-320 clinical trial results: survival data 148 Table 45: Results of a Phase III randomized trial comparing Alimta to Taxotere in second-line treatment of recurrent NSCLC, 2006 149 Table 46: Summary of Tarcevas Phase III BR.21 efficacy data 152 Table 47: Comparison of the efficacy results from pivotal trials which gained Tarceva, Taxotere and Alimta FDA and EMEA approval for second-line NSCLC 153 Table 48: Comparison of the key toxicity results from pivotal trials which gained Tarceva, Taxotere and Alimta FDA and EMEA approval for second-line NSCLC 153 Table 49: Physician rating of unmet needs (1-100) in NSCLC across the seven major markets, 2006 156 Table 50: Summary of Phase III clinical trials involving elderly advanced NSCLC patients 162 Table 51: Preregistration and Phase III NSCLC pipeline, 2006 169 Table 52: NSCLC clinical trial summary: Avastin 171 Table 53: Avastin E4599 Phase II/III clinical trial results 172 Table 54: NSCLC clinical trial summary: Erbitux, 2006 174 Table 55: NSCLC clinical trial summary: Nexavar 176 Table 56: NSCLC clinical trial summary: Zactima 177 Table 57: Physician scoring (1-100) of the likelihood of prescribing key NSCLC pipeline drug-based regimens (1-100), in the seven major markets, 2006 179 Table 58: Physician scoring (1-100) of various drug regimen prescribing for NSCLC patients in 2011, across the seven major markets 185 Table 59: Current use of first-line platinum and non-platinum doublets, triplet regimens, signal transduction and angiogenesis inhibitors for the first-line treatment of all stages of NSCLC, across the seven major markets (%), 2006 189 Table 60: Physician scoring (1-100) of various prescribing scenarios for NSCLC in 2011 across the seven major markets 191 Table 61: Use of first-line drug regimens for stage I/II NSCLC, regardless of whether received as neo-adjuvant and/or adjuvant treatment, across the seven major markets (%), 2006 197 Table 62: Use of first-line drug regimens for stage IIIA NSCLC, across the seven major markets (%), 2006 198 Table 63: Use of first-line drug regimens for stage IIIB NSCLC, across the seven major markets (%), 2006 199 Table 64: Use of first-line drug regimens for stage IV NSCLC in the seven major markets (%), 2006 200 Table 65: Use of second-line drug regimens for the treatment of stages I/II to stage IV NSCLC in the seven major markets (%), 2006 201 Table 66: Use of third-line drug regimens for the treatment of stages I/II to stage IV NSCLC, across the seven major markets (%), 2006 List of Figures Figure 1: Diagrammatic overview of the coverage of the Stakeholder Insight: Non-Small Cell Lung Cancer survey, 2006 21 Figure 2: Population and chemotherapy approach data for NSCLC in the US, 2006 23 Figure 3: Second- and third-line NSCLC drug regimens in the US, 2006 24 Figure 4: Population and chemotherapy approach data for NSCLC in Japan, 2006 25 Figure 5: Second- and third-line NSCLC drug regimens in Japan, 2006 26 Figure 6: Population and chemotherapy approach data for NSCLC in France, 2006 27 Figure 7: Second- and third-line NSCLC drug regimens in France, 2006 28 Figure 8: Population and chemotherapy approach data for NSCLC in Germany, 2006 29 Figure 9: Second- and third-line NSCLC drug regimens in Germany, 2006 30 Figure 10: Population and chemotherapy approach data for NSCLC in Italy, 2006 31 Figure 11: Second- and third-line NSCLC drug regimens in Italy, 2006 32 Figure 12: Population and chemotherapy approach data for NSCLC in Spain, 2006 33 Figure 13: Second- and third-line NSCLC drug regimens in Spain, 2006 34 Figure 14: Population and chemotherapy approach data for NSCLC in the UK, 2006 35 Figure 15: Second- and third-line NSCLC drug regimens in the UK, 2006 36 Figure 16: Anatomy of the human lungs 37 Figure 17: Forecast incidence of lung cancer (types C33 and C34) in the seven major markets, 2002-2016 42 Figure 18: Forecast incidence of NSCLC in the seven major markets, 2002-2016 43 Figure 19: NSCLC patients diagnosed at each stage (I-IV) (%), 2006 47 Figure 20: Mean NSCLC patients suitable for surgery with curative intent, across the seven major markets, (%) 2006 50 Figure 21: Stage I/II NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 52 Figure 22: Stage IIIA NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 54 Figure 23: Stage IIIB NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 56 Figure 24: Stage IV NSCLC patients suitable for surgery with curative intent across the seven major markets (%), 2006 57 Figure 25: Chemotherapy approaches for resectable stage I/II NSCLC patients in the seven major markets (%), 2006 72 Figure 26: Change in chemotherapy approaches between stage IIIA and stage IIIB resectable NSCLC in the seven major markets (%), 2006 76 Figure 27: Chemotherapy approaches for resectable stage IV NSCLC patients in the seven major markets (%), 2006 78 Figure 28: Mean chemotherapy approaches for resectable NSCLC patients between stage I/II and IV, across the seven major markets, 2006 80 Figure 29: Mean use of chemotherapy treatment within non-surgical NSCLC patients between stage I/II and stage IV, across the seven major markets (%), 2006 83 Figure 30: Use of chemotherapy treatment in non-surgical stage IV NSCLC patients in the seven major markets (%), 2006 89 Figure 31: Mean use of first-line single, doublet and triplet chemotherapy regimens for stage I/II-IV NSCLC across the seven major markets (%), 2006 94 Figure 32: Use of first-line single, doublet and triplet chemotherapy regimens for stage IV NSCLC in the seven major markets (%), 2006 97 Figure 33: Mean use of first-line platinum-based regimens from stage I/II-IV, across the seven major markets (%), 2006 101 Figure 34: Use of key first-line drug regimens for stage IV NSCLC in the seven major markets (%), 2006 105 Figure 35: Mean use of platinum-taxane doublets versus platinum-non-taxane third-generation cytotoxic doublets for the treatment of stage I/II-IV NSCLC, across the seven major markets (%), 2006 109 Figure 36: Use of first-line platinum-taxane versus platinum-non-taxane third-generation cytotoxic regimens for the treatment of stage IV NSCLC in the seven major markets (%), 2006 110 Figure 37: Mean use of the top three first-line drug regimens for the treatment of stage I/II-IV NSCLC, across the seven major markets (%), 2006 112 Figure 38: Use of the top three first-line drug regimens for the treatment of stage IV NSCLC (%), 2006 114 Figure 39: Use of the top-three first-line drug regimens for the treatment of stage IV NSCLC (%), 2006 115 Figure 40: Mean use of first-line single-agent regimens for the treatment of stage I/II-IV NSCLC across the seven major markets (%), 2006 120 Figure 41: Mean use of first-line MTT-based regimens for stage I/II-IV NSCLC across the seven major markets (%), 2006 123 Figure 42: Use of first-line MTT-based regimens for stage IV NSCLC in the seven major markets (%), 2006 124 Figure 43: Mean use of first-line Iressa-, Tarceva-, Avastin- and Erbitux-based regimens for the treatment of stage I/II-IV NSCLC, across the seven major markets (%), 2006 126 Figure 44: Use of first-line Iressa, Tarceva, Avastin and Erbitux-based regimens for the treatment of stage IV NSCLC in the seven major markets (%), 2006 128 Figure 45: Use of the top three second-line drug regimens for the treatment of all stages of NSCLC, as a mean of the seven major markets and within the US, Japan and France (%), 2006 131 Figure 46: Use of the top three second-line drug regimens for the treatment of all stages of NSCLC, within Germany, Italy, Spain and the UK (%), 2006 132 Figure 47: Use of the top three third-line drug regimens for the treatment of all stages of NSCLC as a mean of the seven major markets and within the US, Japan and France (%), 2006 135 Figure 48: Use of the top three second-line drug regimens for the treatment of all stages of NSCLC within Germany, Italy, Spain and the UK (%), 2006 136 Figure 49: Mean use of platinum-based and non-platinum-based regimens for the treatment of all stages of NSCLC within the three line settings, across the seven major markets (%), 2006 139 Figure 50: Mean use of molecular targeted for the treatment of all stages of NSCLC, within the three line settings, across the seven major markets (%) 2006 141 Figure 51: Mean use of gefitinib, erlotinib, bevacizumab and cetuximab-based regimens for the treatment of all stages of NSCLC, within the three line settings, across the seven major markets (%), 2006 143 Figure 52: Timeline of the FDA and EMEA approvals of Taxotere, Alimta and Tarceva within NSCLC, 1999-2006 146 Figure 53: Mean physician rating of clinical unmet needs (1-100) in NSCLC, across the seven major markets, 2006 157 Figure 54: Physician rating of clinical unmet needs (1-100) in NSCLC, for the mean, the US, Japan and France, 2006 165 Figure 55: Physician rating of clinical unmet needs (1-100) in NSCLC for the UK, Spain, Italy and Germany, 2006 165 Figure 56: Mean physician scoring (1-100) of the likelihood of prescribing key NSCLC pipeline-based regimens (1-100), across the seven major markets, 2006 179 Figure 57: Physician rating of key NSCLC pipeline-based regimens (1-100) in the seven major markets, 2006 181 Figure 58: Physician scoring (1-100) of various drug regimen prescribing for NSCLC patients in 2011 in the seven major markets 186 Figure 59: Physician scoring (1-100) of various prescribing scenarios for NSCLC in 2011 192