1. Population-based Study Of Giant Cell Tumour Of The Bone In Sweden Justyna Amelio, 1 Julia Sandberg, 2 Rohini K. Hernandez, 3 Patrik Sobocki, 4 Scott Stryker, 4 Jacob Engellau, 5 Bruce A. Bach, 1 Alexander Liede 4 1 Amgen Ltd. Uxbridge, UK; 2 Pygargus/IMS Health, Stockholm, Sweden; 3 Amgen Inc. Thousand Oaks, CA, USA; 4 Amgen Inc. San Francisco, CA, USA; 5 Lund University, Lund, Sweden Presented by Bruce A. Bach, MD

2. Disclosures J Amelio, RK Hernandez, S Stryker, BA Bach, A Liede are employees of and hold stock in Amgen Inc. J Engellau is a consultant for Amgen Inc. J Sandberg, P Sobocki are employees of Pygargus AB and IMS Health

3. GCTB : An Osteoclastogenic Stromal Tumour Epiphyseal lytic lesion Multinuclear giant cells mononuclear stromal cell

4. Objective The primary objective was to estimate the incidence rate (IR) and mortality rates of GCTB as recorded in the Swedish Cancer Registry The study forms part of the post-marketing commitment with the US Food and Drug Administration following June 2013 approval of denosumab in GCTB, to help further the understanding of the epidemiology of this rare condition GCTB, Giant Cell Tumour of Bone

5. Data Sources on GCTB Sources of data on GCTB concerning incidence and prevalence of the disease are quite sparse; most published data are derived from bone tumour registries, institutional case studies or cooperative group trial experience The most recent population-based study was conducted in Sweden and published in 1975 1 The Swedish Cancer Registry offers a unique source to study GCTB as it is one of the few national population- based databases that records GCTB (confirmed by pathologist review) 1 Larsson SE, et al. J Bone Joint Surg Am. 1975;57(2):167–73. GCTB, Giant Cell Tumour of Bone

6. Methods A population-based, retrospective and longitudinal observational study Data are from national compulsory health registries governed by the National Board of Health and Welfare and are representative of the entire Swedish population We identified all patients with a diagnosis of GCTB reported between 1983–2011: –benign (ICD-7 196.0-196.9; PAD 741) –malignant (ICD-7 196.0-196.9; PAD 746)

7. Methods 95% confidence intervals were calculated as a measure of precision around the incidence and mortality rates Prespecified analyses include stratification by age at diagnosis, gender, anatomical lesion location, and rural versus urban residence

8. Results The cohort included 337 patients diagnosed with GCTB between 1983–2011 –Median age of onset was 34 years (range 10–88) –54% (n=183) were female Overall IR was 1.3 per million persons per year* –IR was highest in the 20–29 age group (IR 2.5 per million persons per year) The majority were primary benign cases (n=310; 92%) –IR 1.2 per million persons per year *The average population of Sweden 1983–2011 was estimated to be 8.8 million (Statistics Sweden, http://www.statistikdatabasen.scb.se) GCTB, Giant Cell Tumour of Bone

9. Results (continued) Among primary malignant GCTB, the highest incidence was observed in the 20-39 age group: IR 0.21 per million persons per year (n=15)* –Most frequently this occurred in the lower extremities: IR 0.051 per million persons per year (n=13) Malignant to benign ratio was higher among women 0.095 (16/167) than men 0.077(11/143) For both benign and malignant GCTB the most common lesion site was the lower extremities *The population of Sweden was estimated to be 9 million inhabitants as of 2011 GCTB, Giant Cell Tumour of Bone

10. Incidence rates of primary benign GCTB in rural and urban areas of Sweden 1983-2011 *The population of Sweden was estimated to be 9 million inhabitants as of 2011 GCTB, Giant Cell Tumour of Bone

11. Incidence Rates 1983-2011 per million population /year

12. GCTB incidence by histologic classification (1983-2011) Benign (N=310)Malignant (N=27) Axial (N=33) 0.129 (95%CI: 0.105-0.157) Upper extremity (N=81) 0.0174 (95%CI:0.257-0.384) Pelvic (N=19) 0.074 (95%CI:0,060-0,090) Lower extremity (N=143) 0.558 (95%CI: 0.454-0.679) Not specified (N=34) 0.133 (95%CI:0.108-0.162) Axial (N=2) 0.008 (95%CI:0.001-0.029) Upper extremity (N=4) 0.016 (95%CI:0.004-0.041) Pelvic (N=4) 0.016 (95%CI:0.004-0.041) Lower extremity (N=13) 0.051 (95%CI: 0.027-0.087) Not specified (N=4) 0.016 (95%CI:0.004-0.041) GCTB, Giant Cell Tumour of Bone

13. Mortality : Cumulative Incidence Proportion in GCTB patients (at 5 and 20 year)

14. This is a first comprehensive population-based, retrospective cohort study leveraging national cancer registry data over 28 years that confirmed that GCTB is a rare disease in Sweden Consistent with the published literature: –Primary malignant GCTB cases were uncommon (8%) relative to benign cases –GCTB peak incidence between 20–39 years of age Median age of onset of 34 years –Slight predominance in women (54%) –Most common lesion location was lower extremity (knee) followed by axial skeleton –Higher rates in urban than rural populations Conclusions GCTB, Giant Cell Tumour of Bone

15. The relative observed proportions of the begin/malignant tumours by site of origin (except pelvis) were similar Further work is needed to describe varying treatments and long term outcomes of patients with GCTB Conclusions GCTB, Giant Cell Tumour of Bone

16. Giant Cell Tumour of Bone Giant Cell Tumour of Bone (GCTB) is a predominately histologically benign, locally aggressive, osteoclastogenic neoplasm that generally occurs in young-to-middle aged adults Most common site is in the epiphysis of long bones, but GCTB may develop at any bone site, and is often associated with pain, pathologic fracture and/or invasion of adjacent soft tissues 1 GCTB, the most common histologically benign tumour of the bone, may metastasise in 5%-8% of cases. 2-4 The less common, malignant form of GCTB has a more aggressive phenotype and a poorer prognosis 5,6 1 Larsson SE, et al. J Bone Joint Surg Am. 1975;57(2):167–73; 2 Szendroi M. J Bone Joint Surg Br 2004;86:5–12; 3 Klenke FM, et al. Clin Orthop Relat Res 2011;469:591–9; 4 Campanacci M, et al. J Bone Joint Surg Am. 1987;69:106–114; 5 Bertoni F, et al. Cancer 2003;97:2520–2529; 6 Rock MG, et al. J Bone Joint Surg Am. 1986;68(7):1073–9