1 / 16

Safety and Efficacy of Denosumab for Giant Cell Tumor of Bone

Safety and Efficacy of Denosumab for Giant Cell Tumor of Bone.

aolani
Download Presentation

Safety and Efficacy of Denosumab for Giant Cell Tumor of Bone

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Safety and Efficacy of Denosumab for Giant Cell Tumor of Bone Jean-Yves Blay1; Sant Chawla2; Leanne Seeger3;Robert Henshaw4; Edwin Choy5; Robert Grimer6; Stefano Ferrari7; Peter Reichardt8; Piotr Rutkowski9; Scott Schuetze10; David Thomas11; Antonio Lopez Pousa12; Yi Qian13; Ira Jacobs13 1University Claude Bernard Lyon I, Lyon, France; 2Sarcoma Oncology Center, Santa Monica, CA, USA; 3Musculoskeletal Radiology, UCLA School of Medicine, Los Angeles, CA, USA; 4Georgetown University College of Medicine, Washington, DC, USA; 5Massachusetts General Hospital, Boston, MA, USA; 6Royal Orthopaedic Hospital, Birmingham, UK; 7Istituti Ortopedici Rizzoli, Bologna, Italy; 8HELIOS Klinik Berlin-Buch, Berlin, Germany; 9Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; 10University of Michigan, Ann Arbor, MI; 11Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; 12Hospital Sant Pau, Barcelona, Spain; 13Amgen Inc., Thousand Oaks, CA, USA

  2. Acknowledgements and Disclosures • Funding for the study and assistance with presentation preparation was provided by Amgen Inc. • J. Y. Blay has received corporate-sponsored research funding from and has served as an advisory board member for Novartis, GSK, Roche, MSD, and PharmaMar. • S. Chawla has received corporate-sponsored research funding from and has served as an advisory board member for Amgen, Threshold, Cytrax, GlaxoSmithKline, and Berg Pharma. • R. Henshaw has received corporate-sponsored research funding from and has served as an advisory board member for Amgen. • E. Choy has received research funding from the Liddy Shriver Sarcoma Initiative and has served as a consultant to Amgen, Sanofi-Aventis, and Biomed Valley Discoveries. • S. Ferrari has received funding from Amgen, Molmed, PharmaMar, and Pfizer and received support from Takeda to attend scientific meetings. • P. Reichardt has served as an advisory board member for Novartis, Pfizer, Bayer, MSD/Merck, and as a speakers’ bureau member for Novartis, Pfizer, MSD/Merck, Amgen, and PharmaMar. • P. Rutkowski has served as an advisory board member for Novartis, Bristol-Myers Squib (BMS), and MSD and as a speaker’s bureau member for Novartis, Pfizer, Roche, BMS, and MSD. • D. Thomas has received research support from Amgen Inc. • Y. Qian and I. Jacobs are employees of Amgen Inc. and have received Amgen stock/stock options. • L. Seeger, R. Grimer, S. Schuetze, and A. Lopez Pousa have no relationships to disclose.

  3. Giant Cell Tumor of Bone (GCTB) • Locally aggressive, destructive primary bone tumor • Causes pain and swelling and impairs mobility and function1 • No standard or approved medicinal therapy • Surgical intervention often associated with significant morbidity2 • Mendenhall WM, et al. Am J Clin Oncol. 2006;29:96-9. • Thomas DM, Skubitz KM. Curr Opin Oncol. 2009;21:338-344.

  4. Denosumab in GCTB • GCTB stromal cells, thought to be the neoplastic component of GCTB, express high levels of RANK ligand (RANKL) that stimulate the formation of RANK-positive tumor giant cells from RANK-positive osteoclast precursors.1-6 • High levels of RANKL also stimulate giant cell activation and survival and tumor-induced bone lysis.3-5 • Denosumab is a fully human monoclonal antibody against RANKL.6 • Denosumab inhibits bone destruction by preventing RANKL-mediated formation, activation, and survival of osteoclast-like giant cells.5 Atkins GJ, et al.. J Bone Miner Res. 2006;21:1339-1349. Huang L, et al. Am J Pathol. 2000;156:761-767. Roux S, et al. Am J Clin Pathol. 2002;117:210-21.6 Lau YS et al. Hum Pathol. 2005;36:945–54. Branstetter DG et al. Clin Cancer Res 2012; 8(16):4415-24. Bekker PJ, et al. J Bone Miner Res. 2004;19:1059-66.

  5. Objectives • To evaluate the safety profile of denosumab in patients with GCTB treated with denosumab • To evaluate time to disease progression in patients with unsalvageable GCTB • To evaluate the proportion of denosumab-treated patients with salvageable GCTB who do not require surgery, for whom surgery is delayed, or who are able to undergo a less morbid surgery • This prespecified interim analysis includes all eligible patients enrolled between September 9, 2008 and March 25, 2011 (the analysis cut-off date) • Additional results from this study are being presented in posters at CTOS: • Results of independent imaging assessments (poster 144) • Effects of denosumab on pain and analgesic use (poster 143)

  6. Study Design 1 8 15 2 3 4 5 6 Months 7 to N Denosumab 120 mg SC Adults or skeletally mature adolescents with GCTB • Cohort 1: Surgically unsalvageable GCTB Cohort 2: Salvageable GCTB with planned surgery Cohort 3*: Patients who transitioned from previous denosumab GCTB study *No loading doses on days 8 and 15 N = number of months on study

  7. Results: Study Participation Patients Enrolled: 282 Cohort 1: 170 patients Cohort 2: 101 patients Cohort 3: 11 patients 21 Discontinued Study 2 Complete tumor resection 7 Adverse event 1 Consent withdrawn 1 Disease progression 2 Requirement for alternative therapy 1 Pregnancy 7 Other 20 Discontinued Study 10 Protocol-specific criteria 1 Adverse event 2 Consent withdrawn 2 Disease progression 5 Other 0 Discontinued Study 149 on study at interim analysis cutoff date 81 on study at interim analysis cutoff date 11 on study at interim analysis cutoff date 11 analyzed for efficacy ‡11 analyzed for safety‡ 169 analyzed for efficacy * 169 analyzed for safety * 100 analyzed for efficacy † 101 analyzed for safety † *In cohort 1, 169 patients received investigational product. †In cohort 2, 101 patients received investigational product, but one cohort 2 patient was ineligible (no written informed consent) and was therefore excluded from the efficacy analysis. ‡Cohort 3 patients are included in the safety analyses but not in the efficacy analyses in this presentation.

  8. Results: Baseline Demographics and Disease Characteristics

  9. Results: GCTB Characteristics IV: intravenous • The median number of doses was 13 (range, 1-33). • The median time on study was 10 months (range, 0-29).

  10. Disease Status (Investigator-Determined) Best Response During the Assessment Period Cohort 1: Surgically Unsalvageable (N1 = 159*) Cohort 2: Salvageable, Surgery Planned (N1 = 93*) N1 = number of enrolled patients who were eligible and received ≥ 1 dose of denosumab and had a disease status evaluation. • 6 patients (4%) in Cohort 1 experienced disease progression at some time during the assessment period; the median time to disease progression was not reached.

  11. Clinical Benefit (Investigator-Determined) Best Response During the Assessment Period Cohort 1: Surgically Unsalvageable N1 = 169* Cohort 2: Salvageable, Surgery Planned N1 = 100* N1 = number of enrolled patients who were eligible and received ≥ 1 dose of denosumab.

  12. Radiologic Response to Denosumab Pre-Treatment Week 19 Post-Treatment

  13. Radiologic Response to Denosumab Baseline Week 5 Week 37

  14. Planned Versus Actual Surgery in Cohort 2 * n = number of patients • Of the 71 patients in Cohort 2 who had the opportunity to be on study for ≥6 months, 64 (90%) did not have any surgery by month 6. • By the analysis cut-off date, 74 of 100 patients (74%) in Cohort 2 had not undergone surgery.

  15. Adverse Events Based on Medical Dictionary for Regulatory Activities (MedDRA; version 14.1 and CTCAE version 3.0)* n = number of patients who received ≥ 1 dose of denosumab † By the cutoff date, 2 cases were resolved and 1 case was not resolved

  16. Summary • The safety profile of denosumab in these patients with GCTB was consistent with that observed in other denosumab trials; no new risks were observed • ONJ and hypocalcemia, known risks of denosumab, were observed at a low rate consistent with that seen in other studies • 96% of Cohort 1 patients had no disease progression at any time on study, as determined by the investigator • Of 100 patients for whom surgery was planned: • 74 had no surgery • 16 of 26 had less morbid surgeries than planned • Denosumab delayed disease progression, prolonged the time to surgery, and reduced the need for morbid surgery in most patients, representing a potential new treatment option for patients with GCTB

More Related