Ostenonecrosis of the jaw (ONJ) after denosumab in patients with giant cell tumor of bone (GCTB): a single institution analysis of a prospective, international study 20062004

Background Giant cell tumor of bone (GCTB) is a progressive osteolytic tumor with proven response to denosumab when unresectable or at high surgical risk. We report on incidence of suspected (sONJ) and adjucated (aONJ) osteonecrosis of the jaw cases, from a single institution series of patients treated with denosumab within a phase 2 study  Methods Patients  were enrolled with unresectable GCTB (Cohort 1), resectable GCTB with planned high morbidity surgery (Cohort 2). Denosumab was given 120 mg SC every 4 weeks with loading doses on days 8 and 15. The primary endpoint was safety: aONJ and s ONJ rate; efficacy endpoints included proportion of Cohort 2 patients without surgery, and progression-free survival for all patients Results Baseline characteristics and ONJ results for 52 patients are shown in the Table 1. Median follow-up was 103 months (95%CI 55-126) in Cohort 1 and 105 months (95%CI 94-116) in Cohort 2. Overall response rate was 20% in all sample. Of 9 Cohort 1 patients, 1 ended denosumab for GCTB progression after 70 months of follow-up. Overall Kaplan Meier (KM) estimates (95% CI) for GCTB progression-free in these patients were 88% (39-98%). 23 Cohort 2 pts (53%) ended denosumab without GCTB progression, and 20 (47%) recurred with a KM estimate of 67% (51-79) at 24 months, and 52% (36-66%) at 60 months. Median time of denosumab therapy was 80 months in Cohort 1 and 14 months in Cohort 2. Within Cohort 2 patients with planned surgery, 88% underwent surgery and 12% continued with denosumab only. Following surgery, recurrence occurs higher after curettage than resection (47% vs 5%). ONJ rate is reported in Table 1.  Conclusions Denosumab was generally well tolerated with excellent long-term disease control in unresectable patients. A 47% recurrence rate following surgery was seen in this high-risk, selected, resectable population. Denosumab has major, long-lasting antitumor activity in unresectable or metastatic GCTB, with an aONJ and sONJ rate of 4% and 8%, respectively, in this series.