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 Liede4

1Amgen Ltd. Uxbridge, UK; 2Pygargus/IMS Health, Stockholm, Sweden; 3Amgen Inc. Thousand Oaks, CA, USA; 4Amgen Inc. San Francisco, CA, USA; 5Lund University, Lund, Sweden

Presented by Bruce A. Bach, MD

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

GCTB : An Osteoclastogenic Stromal Tumour

Epiphyseal lytic lesion Multinuclear giant cells mononuclear stromal cell

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

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 19751

• 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)

1Larsson SE, et al. J Bone Joint Surg Am. 1975;57(2):167–73. GCTB, Giant Cell Tumour of Bone

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)

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

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

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 2011GCTB, Giant Cell Tumour of Bone

Incidence rates of primary benign GCTB inrural and urban areas of Sweden 1983-2011

*The population of Sweden was estimated to be 9 million inhabitants as of 2011GCTB, Giant Cell Tumour of Bone

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

0

0.5

1

1.5

2

2.5

3

3.5

Urban Benign GCTB Rural Benign GCTB

Inci

den

ce p

er m

illio

n p

erso

ns

Incidence Rates 1983-2011 per million population /year

malignant

benign

0 0.5 1 1.5 2

0.087

1.128

0.124

1.291

Gender

female male

malignant

benign

0 0.5 1 1.5 2 2.5

0.031

0.669

0.21

1.861

0.073

1.314

0.084

0.737

Age

60+ 40-59 20-39 0-19

malignant

benign

0 0.5 1 1.5 2

0.116

1.535

0.103

0.999

Geographic Location

rural urban

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

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

5-year

20-year

0 0.05 0.1 0.15 0.2 0.25

0.058

0.143

0.044

0.142

Female

Male

5-year

20-year

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4

0.011

0.023

0

0.019

0.063

0.146

0.097

0.323

age 55-64

age 45-54

age 35-44

age 25-34

age 15-24

5-year

20-year

-0.0

5000

0000

0000

001

-9.0

2056

2075

0794

E-17

0.04

9999

9999

9999

99

0.09

9999

9999

9999

990.

15 0.2

0.25 0.

30.

35 0.4

0.45

0.086

0.171

0.043

0.174

0.012

0.129

0.064

0.128

0.013

0.045

Non-spec

Lower extremity

Upper extremity

Pelvic

Axial

• 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

• 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

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 tissues1

• 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 prognosis5,6

1Larsson SE, et al. J Bone Joint Surg Am. 1975;57(2):167–73; 2Szendroi M. J Bone Joint Surg Br 2004;86:5–12; 3Klenke FM, et al. Clin Orthop Relat Res 2011;469:591–9; 4Campanacci M, et al. J Bone Joint Surg Am. 1987;69:106–114; 5Bertoni F, et al. Cancer 2003;97:2520–2529; 6Rock MG, et al. J Bone Joint Surg Am. 1986;68(7):1073–9