Renal function changes and resource use in patients with metastatic bone disease treated with IV zoledronic acid or oral ibandronic acid: Interim results

9630 Background: The bisphosphonate (BP) ZOL is frequently used to prevent skeletal-related events (SRE) in cancer pts. However, data are limited on its use beyond 2 years. LOTUZ is among the first studies to examine Rx and outcomes in pts with ZOL Rx for >2y. We report 6-month results. Methods: Prospective (18m), multicenter (50), pharmacoepidemiologic study. Baseline (0m) and 6m data available on 205 pts (of 298 enrolled), all free from osteonecrosis of the jaw (ONJ) at 0m. Prior to ZOL Rx, 27.8% had non-ZOL BP Rx. Mean pre-enrollment BP duration was 42 mo (23–145) with 38 mo (23–80) for ZOL. Results: Mean age: 64 y (38–88); M/F: 29/71%; 67.8% with MBD vs 32.2% MM. 89.3% continued ZOL RX 0–6m; 90% with dose 4mg. From 0–6m, 10 pts (4.8%) developed ONJ (4 with MM, 6 with MBD): 5 mild, 3 moderate, 2 severe (median BP duration: 38.4, 46.5, and 34.8 months, respectively). Five pts with ONJ continued on ZOL RX 0–6m (3 mild, 2 moderate). 4/10 pts with ONJ had baseline dental conditions or procedures, 8/10 at 6m (only 1/10 at neither). SREs and pain levels remained constant 0–6m compared to 6m prior to baseline (see Table ). Conclusions: Beyond 2y, 90% of pts were continued on ZOL. SREs did not increase, but ONJ was diagnosed in 10/205 pts 0–6m, of which 5 were on ZOL RX beyond 24m. Long-term data are needed to better understand the risk/benefit of long-term ZOL Rx. [Table: see text] [Table: see text]

Download Full-text

Denosumab and zoledronic acid treatment in patients with genitourinary cancers and bone metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5079 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5079-5079 ◽

Cited By ~ 2

Author(s):

Luis Costa ◽

Karim Fizazi ◽

Fred Saad ◽

Janet Elizabeth Brown ◽

Roger Von Moos ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Disease ◽

Proportional Hazards Model ◽

Transitional Cell ◽

Cox Proportional Hazards ◽

Metastatic Bone Disease ◽

Cox Proportional Hazards Model ◽

Phase Iii ◽

Pivotal Phase ◽

Significant Difference

5079 Background: Phase III trial results showed that denosumab is superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) in patients with cancer and metastatic bone disease (Lipton et al; 2012, Eur J Cancer). Genitourinary (GU) cancers are some of the most commonly diagnosed cancers worldwide. We now compare the efficacy and safety of denosumab (DMAb) or ZA in a subgroup analysis of patients with GU cancers enrolled in the pivotal phase III trials. Methods: Patients were randomized 1:1 to receive DMAb (120 mg, SC) or ZA (4 mg, IV, adjusted for renal function) every 4 weeks. Daily calcium and vitamin D supplements were strongly recommended. Time to 1st on-study SRE, using a Cox proportional hazards model, time to 1st and subsequent on-study SRE, using the Anderson-Gill model, and safety were evaluated for the GU subgroup in an ad hoc analysis. Results: 2,128 patients (1,052 DMAb; 1,076 ZA) had GU cancers (prostate = 1,901, renal = 155, bladder = 63, and transitional cell = 9). DMAb significantly delayed the time to 1st on-study SRE by 4.0 months compared with ZA (20.7 months vs 16.7 months) in patients with GU cancers (Table). DMAb also significantly delayed the time to 1st and subsequent on-study SRE. Time to disease progression and overall survival were similar between treatment groups. Adverse events (AEs) and serious AEs were reported by similar percentages of patients in both groups (AEs: 96.9% denosumab, 96.8% ZA; serious AEs: 62.8% denosumab, 60.2% ZA). 14.6% of DMAb pts and 15.9% of ZA pts had a renal AE. Hypocalcemia was reported for 12.9% of DMAb patients and 6.2% of ZA patients. There was no significant difference in the incidence of positively adjudicated osteonecrosis of the jaw between the DMAb (2.2%) and ZA (1.6%) groups (p=0.34). Conclusions: Among patients with GU cancers and metastatic bone disease, DMAb was superior to ZA in preventing SREs. Clinical trial information: NCT00330759 and NCT00321620. [Table: see text]

Download Full-text