Stakeholder Opinions Head and Neck Cancer

CHAPTER 1 EXECUTIVE SUMMARY - 3

Scope of the analysis - 3

Datamonitor insight into the head and neck cancer market - 3

Related reports - 4

Upcoming reports - 4

CHAPTER 2 HEAD AND NECK CANCER OVERVIEW - 6

Introduction - 6

Anatomy of the head and neck - 7

Symptoms of head and neck cancer - 7

Subtypes - 8

Paranasal sinuses and nasal cavity cancers - 9

Oral cavity cancers - 10

Salivary gland cancer - 11

Pharyngeal cancers - 11

Laryngeal cancers - 12

Staging head and neck cancer - 12

Tumor, nodes and metastasis classification for head and neck cancer - 13

Risk factors in head and neck cancer - 15

Tobacco and alcohol independently increase risk - 15

Human papilloma virus exposure - 15

Diet may be important in nasopharyngeal cancer - 16

Epidemiology - 17

Crude incidence rates for head and neck cancers - 17

Incidence of head and neck cancer by gender in 2007 - 18

Head and neck cancer is more prevalent in males - 18

Forecast incidence for head and neck cancer by subtype to 2016 - 19

Incidence of head and neck cancer subtypes by country in 2007 - 20

Oral cancers account for 44% of all head and neck cancers across the 7MM - 20

Human papilloma virus may increase head and neck cancer incidence - 21

CHAPTER 3 CURRENT TREATMENT OPTIONS FOR HEAD AND NECK CANCER - 22

Head and neck cancer treatment overview - 22

Radiotherapy is the cornerstone of head and neck cancer treatment - 24

Intensity modulated radiation therapy - 25

Chemoradiotherapy (CRT): cisplatin sets the standard - 25

Single-agent based chemoradiotherapy (CRT) - 26

Multi-agent based chemoradiotherapy (CRT) - 27

Cisplatin, 5-flurouracil and radiotherapy - 27

Cisplatin, paclitaxel and radiotherapy - 27

5-fluorouracil, hydroxyurea and radiotherapy (FHX) - 28

Paclitaxel, 5-fluorouracil, hydroxyurea and radiotherapy (TFHX) - 28

Can induction chemotherapy control distant metastasis? - 28

Taxotere sets a new induction standard - 29

Paclitaxel-based induction therapy - 31

Erbitux advances SCCHN treatment - 31

Clinical trial results for Erbitux in SCCHN - 33

Phase III Erbitux trial meets primary endpoint - 34

Bristol-Myers Squibb/ImClone/Merck Serono anticipate further Erbitux efficacy data - 35

HPV status may influence choice of SCCHN treatment - 37

CHAPTER 4 UNMET NEEDS & TREATMENT CONTROVERSIES IN HEAD AND NECK CANCER - 39

Intolerable toxicities associated with current treatment options - 39

Poor outcome still remains for patients with metastatic disease - 41

Current SCCHN treatment requires standardization - 42

Identifying responder groups for targeted therapy in SCCHN - 43

Conclusions - 43

CHAPTER 5 HEAD AND NECK CANCER PRODUCT PIPELINE - 44

Head and neck cancer pipeline overview - 44

Pipeline overview - 45

Late-phase product pipeline for head and neck cancer - 45

Phase II product pipeline for head and neck cancer - 45

Phase I product pipeline for head and neck cancer - 48

Late-phase cytotoxic drug profile - 49

Lipoplatin (Regulon) - 49

Drug overview - 49

Key historical events - 49

Clinical trial data - 50

Datamonitor comments - 51

Late-phase molecular targeted therapy drug profiles - 52

Proxinium (VB4-845; Viventia Biotech) - 52

Drug overview - 52

Key historical events - 53

Clinical trial data - 54

Datamonitor comments - 56

Tykerb (lapatinib; GlaxoSmithKline) - 57

Drug overview - 57

Key historical events - 57

Clinical trial data - 58

Datamonitor comments - 61

Vectibix (panitumumab; Amgen), - 62

Drug overview - 62

Key historical events - 62

Clinical trial data - 63

Datamonitor comments - 66

Zalutumumab (HuMax-EGFr; Genmab) - 66

Drug overview - 66

Key historical events - 67

Clinical trial data - 68

Datamonitor comments - 70

Late-phase gene therapy drug profile - 71

Advexin (INGN-201; Introgen Therapeutics) - 71

Drug overview - 71

Key historical events - 72

Clinical trial data - 73

Datamonitor comments - 74

APPENDIX - 76

Bibliography - 76

Journals - 76

Websites - 82

Other - 84

Key opinion leaders - 84

Abbreviations - 85

List of tables - 86

List of figures - 87

About Datamonitor - 88

About Datamonitor Healthcare - 88

About the Oncology analysis team - 89

Disclaimer - 89

List of Tables - Table 1: AJCC nodes and metastasis classification for head and neck cancer - 13

Table 2: AJCC primary tumor classification of head and neck cancers - 14

Table 3: Crude incidence rates (per 100,000) of head and neck cancers, 2002 - 17

Table 4: Forecast incidence of head and neck cancers, 2002-2016 - 19

Table 5: Overview of chemotherapy regimens commonly used in combination with radiotherapy in head and neck cancer - 25

Table 6: A randomized study of adjuvant treatment with cisplatin-based chemoradiotherapy versus radiotherapy alone in 167 patients - 26

Table 7: Overview of cisplatin-5-FU-based chemoradiotherapy regimens for SCCHN - 27

Table 8: A Phase III RTOG trial of Erbitux with cisplatin-based CRT for the first-line treatment of patients with locally advanced SCCHN - 37

Table 9: Treatment-related toxicities in SCCHN - 39

Table 10: Pipeline drugs in Phase III development for head and neck cancer, 2007 - 45

Table 11: Pipeline drugs in Phase II development for head and neck cancer, 2007 - 46

Table 12: Pipeline drugs in Phase I development for head and neck cancer, 2007 - 48

Table 13: Lipoplatin: Key historical events - 49

Table 14: Ongoing clinical trials for Lipoplatin in advanced head and neck cancer, 2007 - 50

Table 15: Proxinium: Key historical events - 53

Table 16: Ongoing clinical trials involving Proxinium in head and neck cancer, 2007 - 54

Table 17: Tykerb: Key historical events - 57

Table 18: Tykerb clinical trials in head and neck cancer, 2007 - 59

Table 19: Vectibix: Key historical events - 62

Table 20: Vectibix clinical trials in head and neck cancer, 2007 - 63

Table 21: Zalutumumab: Key historical events - 67

Table 22: Ongoing clinical trials for zalutumumab in head and neck cancer, 2007 - 68

Table 23: Phase I/II study results of zalutumumab in recurrent SCCHN - 69

Table 24: Advexin: Key historical events - 72

Table 25: Ongoing clinical trials for Advexin in head and neck cancer, 2007 - 73

Table 26: Abbreviations used in Stakeholder Opinions: Head and Neck Cancer, 2007 - 85

List of Figures - Figure 1: Anatomy of the head and neck - 7

Figure 2: Positioning of the paranasal sinuses - 9

Figure 3: The three major salivary glands - 11

Figure 4: Subdivisions of the pharynx - 12

Figure 5: Incidence of head and neck cancers by gender, 2007 - 18

Figure 6: Incidence trends of head and neck cancer subtypes, 2002-2016 - 19

Figure 7: Incidence of head and neck cancer subtypes in the seven major pharmaceutical markets, 2007 - 20

Figure 8: Treatment algorithm for SCCHN - 23

Figure 9: A randomized Phase III trial of Taxotere-based induction chemotherapy in patients with Stage III/IV SCCHN - 30

Figure 10: Preliminary Phase III trial results for paclitaxel induction therapy and CRT in 384 locally advanced SCCHN patients - 31

Figure 11: Phase III trial results for Erbitux and radiotherapy in the first-line treatment in patients with Stage III/IV SCCHN - 33

Figure 12: Phase III trial results for Erbitux and chemotherapy in the first-line treatment of recurrent/metastatic SCCHN patients - 34

Figure 13: Phase II trial results for Erbitux and cisplatin-based chemoradiotherapy in the first-line treatment of locoregionally advanced SCCHN - 36

Figure 14: 5-year survival rates (%) for SCCHN patients according to disease stage - 41

Figure 15: Preliminary Phase III results for Lipoplatin in advanced head and neck cancer - 51

Figure 16: Phase I results for Proxinium in advanced SCCHN - 55

Figure 17: Phase II results of Tykerb in recurrent/metastatic SCCHN - 60

Figure 18: Preliminary Phase I results for Vectibix in late-stage head and neck cancer - 65

Figure 19: Phase II trial results for Advexin in recurrent SCCHN - 74