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Loading-dose ibandronate with maintenance dosing for the palliation of metastatic bone pain: The Bon-I-Pain and Bon-O-Pain trials
ABSTRACTS / Bone 38 (2006) S65 – S87
breast cancer patients only (n = 274). Overall, fewer patients experienced adverse events (AEs) with intravenous or oral ibandronate than with zoledronic acid (trial A: 64% vs 74%; trial B: 65% vs 76%). In particular, the incidence of AEs on Days 1 – 3 was lower for ibandronate than zoledronic acid (trial A: 26% vs 47%; trial B: 8% vs 47%). This was mainly because of a zoledronic acid-associated acute-phase response (APR); pyrexia or flu-like symptoms with ibandronate or zoledronic acid were 13% vs 26% in trial A, and 1% vs 27% in trial B. Serious AEs and withdrawal rates were similar between treatment groups. In these comparative studies, fewer patients experienced AEs with ibandronate than zoledronic acid, regardless of ibandronate formulation or dosing schedule. In particular, there was a lower incidence of APR AEs for ibandronate than zoledronic acid, even with intravenous ibandronate treatment.
S69
monitoring will be similarly performed in all patients. Both trials are recruiting and are due to finish in 2007. doi:10.1016/j.bone.2006.01.013
68 Oral ibandronate and intravenous zoledronic acid in metastatic breast cancer patients: Comparative bone turnover marker and safety data J.J. Body a, M. Lichinitser b, R.E. Coleman c, B. Bergstro¨m d a Institut Jules Bordet, Universite´ Libre de Bruxelles, Brussels, Belgium b NN Blokhin Russian Cancer Research Centre, Moscow, Russia c Weston Park Hospital, Sheffield, UK d Hoffmann-La Roche Inc., Nutley, New Jersey, USA
doi:10.1016/j.bone.2006.01.012
67 Loading-dose ibandronate with maintenance dosing for the palliation of metastatic bone pain: The Bon-I-Pain and Bon-O-Pain trials J.J. Body a, J. Gralow b, B. Bergstro¨m c On behalf of the Bon-I-Pain/Bon-O-Pain Investigators a Institut Jules Bordet, Universite´ Libre de Bruxelles, Brussels, Belgium b University of Washington, Seattle, Washington, USA c Hoffmann-La Roche Inc., Nutley, New Jersey, USA Metastatic bone pain (MBP) is the most common and disabling symptom of metastatic bone disease. Phase II studies suggest that high-dose intravenous ibandronate administered over 3 –4 consecutive days (loading-dose) can provide rapid relief from severe or opioid-resistant MBP. Ibandronate is the only bisphosphonate where renal safety issues do not prohibit this intensive dosing schedule. The Bon-I-Pain and Bon-OPain trials are randomized, multicenter, double-blind, doubledummy, 24-week phase III studies comparing loading-dose ibandronate with zoledronic acid treatment for MBP relief. Each trial will recruit 450 patients with advanced cancer (various types) and moderate-to-severe MBP (visual analog scale score 5). In both trials, the ibandronate group will receive intravenous ibandronate 6 mg (15-minute infusion) on Days 1, 2, and 3, and the zoledronic acid group will receive a single 4 mg infusion on Day 1 and dummy infusions on Days 2 and 3 (zoledronic acid product labeling prohibits doses higher than 4 mg). In the Bon-I-Pain trial, maintenance dosing is intravenous ibandronate 6 mg or zoledronic acid 4 mg every 3 –4 weeks. In the Bon-O-Pain trial, maintenance dosing is oral ibandronate 50 mg daily with dummy infusions every 3 –4 weeks, or intravenous zoledronic acid 4 mg every 3– 4 weeks with dummy tablets daily. The primary endpoint is percentage of patients with pain relief. Secondary endpoints include duration and time to onset of pain relief, analgesic use, and patient quality of life. Because of trial blinding, renal
Ibandronate is a single-nitrogen, non-cyclic bisphosphonate. In phase III trials, both intravenous and oral ibandronate decreased the incidence of skeletal complications to a similar extent, and tolerability profiles were comparable to placebo. Bone turnover markers are prognostic indicators of skeletal events. In this 12-week, head-to-head, randomized, open-label, phase III trial, breast cancer patients with confirmed bone lesions received either oral ibandronate 50mg daily (n = 128) or intravenous zoledronic acid 4mg (n = 126) every 4 weeks. The primary endpoint was change in serum type I collagen C-terminal telopeptide (S-CTX) concentration. Other bone markers were also assessed (urinary CTX, serum BAP, P1NP, osteocalcin). Treatment with oral ibandronate was associated with comparable and statistically non-inferior reductions in bone marker levels to intravenous zoledronic acid. In addition, the number of patients with high S-CTX levels at baseline that were normalized during treatment were 26/26 (100%) for ibandronate and 19/22 (86.4%) for zoledronic acid. In safety monitoring, a lower proportion of patients experienced adverse events (AEs) with ibandronate than with zoledronic acid (65% vs 76%). In particular, there was a lower incidence of AEs during the first 3 days of the study (8% vs 47%), explained by fewer acute-phase response AEs, and fewer study withdrawals (2.9% vs 5.1%). Overall, the data show that a convenient oral ibandronate dose of 50 mg/day has a similar efficacy to intravenous zoledronic acid for suppressing tumor-induced bone resorption, but with a superior tolerability profile. doi:10.1016/j.bone.2006.01.014
69 Ibandronate relieves pain and improves quality of life in breast cancer patients with metastatic bone disease: Phase III data J.J. Body a, B. Bergstro¨m b a Institut Jules Bordet, Universite´ Libre de Bruxelles, Brussels, Belgium b Hoffmann-La Roche Inc., Nutley, New Jersey, USA
breast cancer patients only (n = 274). Overall, fewer patients experienced adverse events (AEs) with intravenous or oral ibandronate than with zoledronic acid (trial A: 64% vs 74%; trial B: 65% vs 76%). In particular, the incidence of AEs on Days 1 – 3 was lower for ibandronate than zoledronic acid (trial A: 26% vs 47%; trial B: 8% vs 47%). This was mainly because of a zoledronic acid-associated acute-phase response (APR); pyrexia or flu-like symptoms with ibandronate or zoledronic acid were 13% vs 26% in trial A, and 1% vs 27% in trial B. Serious AEs and withdrawal rates were similar between treatment groups. In these comparative studies, fewer patients experienced AEs with ibandronate than zoledronic acid, regardless of ibandronate formulation or dosing schedule. In particular, there was a lower incidence of APR AEs for ibandronate than zoledronic acid, even with intravenous ibandronate treatment.
S69
monitoring will be similarly performed in all patients. Both trials are recruiting and are due to finish in 2007. doi:10.1016/j.bone.2006.01.013
68 Oral ibandronate and intravenous zoledronic acid in metastatic breast cancer patients: Comparative bone turnover marker and safety data J.J. Body a, M. Lichinitser b, R.E. Coleman c, B. Bergstro¨m d a Institut Jules Bordet, Universite´ Libre de Bruxelles, Brussels, Belgium b NN Blokhin Russian Cancer Research Centre, Moscow, Russia c Weston Park Hospital, Sheffield, UK d Hoffmann-La Roche Inc., Nutley, New Jersey, USA
doi:10.1016/j.bone.2006.01.012
67 Loading-dose ibandronate with maintenance dosing for the palliation of metastatic bone pain: The Bon-I-Pain and Bon-O-Pain trials J.J. Body a, J. Gralow b, B. Bergstro¨m c On behalf of the Bon-I-Pain/Bon-O-Pain Investigators a Institut Jules Bordet, Universite´ Libre de Bruxelles, Brussels, Belgium b University of Washington, Seattle, Washington, USA c Hoffmann-La Roche Inc., Nutley, New Jersey, USA Metastatic bone pain (MBP) is the most common and disabling symptom of metastatic bone disease. Phase II studies suggest that high-dose intravenous ibandronate administered over 3 –4 consecutive days (loading-dose) can provide rapid relief from severe or opioid-resistant MBP. Ibandronate is the only bisphosphonate where renal safety issues do not prohibit this intensive dosing schedule. The Bon-I-Pain and Bon-OPain trials are randomized, multicenter, double-blind, doubledummy, 24-week phase III studies comparing loading-dose ibandronate with zoledronic acid treatment for MBP relief. Each trial will recruit 450 patients with advanced cancer (various types) and moderate-to-severe MBP (visual analog scale score 5). In both trials, the ibandronate group will receive intravenous ibandronate 6 mg (15-minute infusion) on Days 1, 2, and 3, and the zoledronic acid group will receive a single 4 mg infusion on Day 1 and dummy infusions on Days 2 and 3 (zoledronic acid product labeling prohibits doses higher than 4 mg). In the Bon-I-Pain trial, maintenance dosing is intravenous ibandronate 6 mg or zoledronic acid 4 mg every 3 –4 weeks. In the Bon-O-Pain trial, maintenance dosing is oral ibandronate 50 mg daily with dummy infusions every 3 –4 weeks, or intravenous zoledronic acid 4 mg every 3– 4 weeks with dummy tablets daily. The primary endpoint is percentage of patients with pain relief. Secondary endpoints include duration and time to onset of pain relief, analgesic use, and patient quality of life. Because of trial blinding, renal
Ibandronate is a single-nitrogen, non-cyclic bisphosphonate. In phase III trials, both intravenous and oral ibandronate decreased the incidence of skeletal complications to a similar extent, and tolerability profiles were comparable to placebo. Bone turnover markers are prognostic indicators of skeletal events. In this 12-week, head-to-head, randomized, open-label, phase III trial, breast cancer patients with confirmed bone lesions received either oral ibandronate 50mg daily (n = 128) or intravenous zoledronic acid 4mg (n = 126) every 4 weeks. The primary endpoint was change in serum type I collagen C-terminal telopeptide (S-CTX) concentration. Other bone markers were also assessed (urinary CTX, serum BAP, P1NP, osteocalcin). Treatment with oral ibandronate was associated with comparable and statistically non-inferior reductions in bone marker levels to intravenous zoledronic acid. In addition, the number of patients with high S-CTX levels at baseline that were normalized during treatment were 26/26 (100%) for ibandronate and 19/22 (86.4%) for zoledronic acid. In safety monitoring, a lower proportion of patients experienced adverse events (AEs) with ibandronate than with zoledronic acid (65% vs 76%). In particular, there was a lower incidence of AEs during the first 3 days of the study (8% vs 47%), explained by fewer acute-phase response AEs, and fewer study withdrawals (2.9% vs 5.1%). Overall, the data show that a convenient oral ibandronate dose of 50 mg/day has a similar efficacy to intravenous zoledronic acid for suppressing tumor-induced bone resorption, but with a superior tolerability profile. doi:10.1016/j.bone.2006.01.014
69 Ibandronate relieves pain and improves quality of life in breast cancer patients with metastatic bone disease: Phase III data J.J. Body a, B. Bergstro¨m b a Institut Jules Bordet, Universite´ Libre de Bruxelles, Brussels, Belgium b Hoffmann-La Roche Inc., Nutley, New Jersey, USA