Effects of denosumab on pain reduction in giant cell tumor of bone (GCTB): Interim phase II study results.

Abstract

10037 Background: GCTB is a rare disease in which osteoclast-like giant cells and mononuclear cells express RANKL, a mediator of osteoclast activation. Symptoms include localized tenderness, swelling, and often severe, intractable pain. Denosumab is a fully human monoclonal antibody that binds RANKL to inhibit osteoclast-mediated bone destruction. In a previous phase 2 study, 86% of patients with GCTB responded to denosumab. This prespecified analysis of interim 12-month data from a second phase 2 study describes the effects of denosumab on pain in patients with GCTB. Methods: Adult and skeletally mature adolescent patients with GCTB (N=158) received subcutaneous denosumab 120 mg every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15. The Brief Pain Inventory (BPI) Short Form (0-10) was administered before each dose. This analysis includes the 99 patients who received ≥1 dose of denosumab, were on study for ≥6 months, and completed ≥1 BPI assessment. Analyses included the proportion of patients with clinically meaningful reduction in worst pain (≥2‐point decrease in patients with baseline BPI score ≥2 points), proportion of patients with no/mild worst pain at baseline who reported moderate/severe worst pain (>4 points), and change from baseline in analgesic score (0 [no analgesics]–7 [strong opioids, >600mg oral morphine equivalent/day]). Results: Clinically meaningful reduction (≥2-point decrease) in worst pain was reported within 1 week of their first treatment for 32% (19/60) of patients. In addition, 66% (36/55) patients had clinically meaningful reduction in worst pain at week 9. Through week 61, 22% or fewer of patients who had no/mild pain at baseline reported moderate/severe pain (>4 points). Mean analgesic score change from baseline by visit remained constant over time and ranged from ‐0.2 to 0.1 (median 0.0, Q1 0.0, Q3 0.0). Conclusions: In this interim analysis, denosumab use in GCTB was associated with clinically meaningful reduction in worst pain in the majority of patients and the prevention of worsening pain. The reduction in worst pain and prevention of pain worsening were not accompanied by increased analgesic use.