Assessment of Surgical Downstaging in an Open-Label Phase 2 Trial of Denosumab in Patients with Giant Cell Tumor of Bone

Abstract

Annals of Oncology 25 (Supplement 4): iv494–iv510, 2014 doi:10.1093/annonc/mdu354.8 sarcoma 1419PD ASSESSMENT OF SURGICAL DOWNSTAGING IN AN OPEN-LABEL PHASE 2 TRIAL OF DENOSUMAB IN PATIENTS WITH GIANT CELL TUMOR OF BONE Aim: Surgical resection, the standard treatment for giant cell tumor of bone (GCTB), may be associated with severe morbidity and may not be curative for all lesions. In an open-label phase 2 study, treatment with denosumab was associated with delayed surgery and/or a less morbid procedure in most patients with resectable GCTB. We report an unplanned, interim analysis of surgical downstaging in patients with Table: 1419PD abstracts Actual On-Study Procedure Planned Procedure Curettage (n=80) Marginal Excision (n=3) En Bloc Excision (n=1) Hemipelvectomy (n=10) Amputation (n=40) Joint/prosthesis replacement (n=25) Joint resection/fusion (n=35) En bloc resection (n=85) En bloc excision (n=8) Marginal excision (n=1) Curettage (n=18) En Bloc Resection (n=20) Joint Resection/ Fusion (n=5) Joint/Prosthesis Replacement (n=6) Amputation (n=1) © European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. Downloaded from http://annonc.oxfordjournals.org/ at University of California, Los Angeles on August 31, 2015 S. Ferrari 1 , P. Rutkowski 2 , R.J. Grimer 3 , P.D. Stalley 4 , S.P.D. Dijkstra 5 , A. Pienkowski 2 , G. Vaz 6 , L.L. Seeger 7 , A. Feng 8 , B.A. Bach 9 Chemotherapy Unit, Istituto Ortopedico Rizzoli, Bologna, ITALY Soft Tissue/bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, POLAND Orthopaedic Oncology Unit, Royal Orthopaedic Hospital, Birmingham, UK Department of Orthopaedic Surgery, Royal Prince Alfred Hospital, Sydney, NSW, AUSTRALIA Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, NETHERLANDS Department of Orthopedic Surgery, Edouard Herriot Hospital, Lyon, FRANCE Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA Global Development Oncology Therapeutics, Amgen Inc., Thousand Oaks, CA, USA resectable GCTB whose initially planned surgery was expected to result in severe morbidity. Methods: Adults or skeletally mature adolescents with resectable GCTB received denosumab 120 mg SC every 4 weeks and on study days 8 and 15. Planned and actual GCTB surgical procedures after treatment are reported. Procedure selection and timing were based on review of radiographic imaging and clinical response. Results: Overall, 222 patients enrolled and were evaluable for surgical downstaging (men, 46%; median age, 34 y); most had lesions in the lower (n=117) and upper (n=62) extremities or pelvis/sacrum (n=33). In total, 190 (86%) patients had either no surgery (n=106; 48%) or a less morbid procedure (n=84; 38%). All 222 patients received denosumab; median (range) time on denosumab was 14.1 (1.0−57.1) months for all patients and 18.4 (1.0−57.1) months for the 106 patients with no surgery. The proportions of patients with a planned surgical procedure who did not undergo surgery were: hemipelvectomy (n=8/10; 80%), amputation (n=32/40; 80%), joint/prosthesis replacement (n=6/25; 24%), joint resection/fusion (n=14/35; 40%), en bloc resection (n=31/85; 36%), en bloc excision (n=7/8; 88%), curettage (n=8/18; 44%). The native joint preservation rate was 96% in the 25 patients with a planned joint/prosthesis replacement and 86% in 35 patients with a planned joint resection/ fusion. Conclusions: Consistent with initial results, treatment with denosumab was associated with avoidance of invasive surgery or a less morbid procedure than was planned in most patients with resectable GCTB. Disclosure: S. Ferrari: Advisory board (Amgen Inc., GlaxoSmithKline); research funding (MolMed, Pharmar, Morphotek, Amgen Inc.); honoraria (Takeda); P. Rutkowski: honoraria for lectures (Amgen Inc.); R.J. Grimer: Advisory board (Amgen Inc.); S.P.D. Dijkstra: advisory board (Implantcast GmbH); L.L. Seeger: honoraria for advisory boards and travel expenses (Amgen Inc.); A. Feng: employment by and stock ownership in Amgen Inc.; B.A. Bach: employment by and stock ownership in Amgen Inc. All other authors have declared no conflicts of interest.