1480PD - Efficacy and Safety of Denosumab in Giant Cell Tumor of Bone: Updated Results with Independent Radiographic Assessment of Response

Abstract

ABSTRACT Giant cell tumor of bone (GCTB) is an aggressive osteolytic tumor that causes substantial morbidity. We present data from a second open label phase 2 study of denosumab in GCTB. Patients (pts) with surgically unresectable GCTB (Cohort 1), resectable GCTB with planned surgery (Cohort 2), and pts who transferred from the first phase 2 study (Cohort 3) received SC denosumab (120 mg, Q4W), with additional doses on days 8 and 15 (Cohorts 1–2). Prespecified efficacy and safety analyses included all pts who received denosumab. Radiographic assessments of tumor response included pts with ≥1 evaluable time point response (TPR); assessments included RECIST (lesion size), EORTC (PET Standardized Uptake Value by Body Weight [SUVbw]), and Density/Size (CT Hounsfield units). Pts (N = 282) were 58% women, mean age 36 (SD 13) years; 46% had recurrent unresectable disease. AEs were reported in 236 pts (84%); most frequent were arthralgia 20%; headache 18%; nausea 17%; fatigue 16%; back pain 15%; and extremity pain 15%. Osteonecrosis of the jaw was reported in 3 pts (1%). One pt died of respiratory failure, not denosumab-related. Hypocalcemia was reported in 15 pts (5%): 14, grade 1 or 2; 1, grade 3 not deemed clinically significant by the investigator. Of 100 pts in Cohort 2, 90% had no surgery or less morbid surgery than planned. Radiologic analyses included 190 pts. An objective complete or partial tumor response was observed in 72% of pts based on best response, any criteria. Of pts with ≥1 objective tumor response, response rates were 25% with RECIST, 96% with EORTC, and 76% with Density/Size criteria. Among pts with ≥1 evaluable TPR, the median time to objective tumor response was 3.1 months (95% CI 2.89, 3.65) based on best response using any tumor response criteria. Among pts with ≥2 evaluable TPRs ≥12 weeks apart, 96% had tumor control sustained ≥12 weeks based on the best response using any tumor response criteria. Eleven pts (6%) had disease progression. Conclusion: Denosumab appeared to be well tolerated in pts with GCTB, reduced requirements for morbid surgery, and provided a durable objective radiologic response for the majority of pts. Denosumab continues to be studied as a potential treatment for GCTB. Disclosure J. Blay: JY Blay has served as an advisory board member for Novartis, GSK, Roche, MSD, and Pharmamar. He has conducted corporate-funded research for Novartis, GSK, Roche, MSD, and Pharmamar. S. Chawla: Sant Chawla has been an advisory board member for and has received corporate-sponsored research funding from Amgen, Threshold, Cytrax, Glaxxo, and Berg Pharma. E. Choy: E. Choy has served as an advisory board member for Amgen, Sanofi-Aventis, and Biomed Valley Discoveries. S. Ferrari: S. Ferrari has received funds from: AMGEN, MOLMED, PharmaMar, and Pfizer. He received funds for participation to scientific meetings from Takeda. P. Reichardt: P. Reichardt has received honoraria for lectures from Amgen Inc. P. Rutkowski: P. Rutkowski has served as an advisory board member for Norvartis, BMS, and MSD. He has also received honoraria for lectures and travel grants from Novartis, Pfizer, Roche, BMS, and MSD. D. Thomas: David Thomas conducts corporate-sponsored research with Pfizer and AMGEN. Y. Qian: Y. Qian is an employee and stockholder of Amgen Inc. I. Jacobs: I. Jacobs is an employee and stockholder of Amgen Inc. All other authors have declared no conflicts of interest.