Table 1.
Key antiresorptive therapy clinical trials for prevention of skeletal-related events in advanced cancer
| Antiresorptive therapy | N | Dosing | Comparator | Results |
|---|---|---|---|---|
| Prostate cancer | ||||
| ZOL14 | 422a | 4 mg IV q 3–4 wk | Placebo | ↑ Median time to 1st on-study SRE (not reached ZOL vs 321 days placebo; P = 0.011) ↓ In proportion of patients with SREs (44.2% ZOL vs 33.2% placebo; P = 0.021) |
| Dmab4 | 1904 | 120 mg SC q 4 wk | ZOL 4 mg IV q 4 wk | Additional 18% ↑ in time to 1st on-study SRE (P = 0.008; superiority) |
| Breast cancer | ||||
| ZOL15 | 227 | 4 mg IV q 3–4 wk | Placebo | 41% ↓ in SRE risk (P = 0.019)b; 13.5% ↓ in fractures |
| Dmab9 | 2046 | 120 mg SC q 4 wk | ZOL 4 mg IV q 4 wk | Additional 18% ↑ in time to 1st on-study SRE (P = 0.01) |
| PAM10 | 751 | 90 mg IV q 3–4 wk | Placebo | 23% ↓ in SRE risk (P < 0.001)b; 12% ↓ in pathologic fractures (P = 0.002) |
| Ibandronate16 | 312 | 6 mg IV q 3–4 wk | Placebo | 18% ↓ in SRE risk (P = 0.03)b; ↓ vertebral fractures (P = 0.023) |
| Ibandronate17 | 564 | 50 mg PO qd | Placebo | 14% ↓ in SRE risk (P = 0.08)b; no significant difference in number of fractures |
| CLO18–20 | 422 | 1600 mg PO qd | Placebo | 31%, 17%, 8% ↓ in SRE risk respectively (P = 0.03, pooled)b; ↑ time to 1st fracture (P = 0.023) (Kristensen et al18), ↓ vertebral fractures (P < 0.025) (Paterson et al19) |
| Other solid tumors or multiple myeloma | ||||
| ZOL (BC or MM)6,21 | 1116c | 4 mg IV q 3–4 wk | PAM 90 mg IV q 3–4 wk |
Additional 20% ↓ in SRE risk (P = 0.025); 7% ↓ in pathologic fractures (P ≤ 0.05) |
| ZOL (OST)7,22 | 507a | 4 mg IV q 3–4 wk | Placebo | ↑ Median time to 1st on-study SRE (236 days ZOL vs 155 days placebo; P = 0.01); 31% ↓ in SRE risk (P = 0.003) |
| ZOL (MM)23,24 | 1960 | 4 mg IV q 3–4 wk | CLO 1600 mg PO qd | ↓ Proportion of patients with an SRE (27.0% ZOL vs 35.3% CLO; P = 0.0004) 16% ↓ in mortality (P = 0.0118), ↑ median OS 5.5 mo (P = 0.04), 12% ↑ in PFS (P = 0.0179) |
| Dmab (OST or MM)5 | 1776 | 120 mg SC q 4 wk | ZOL 4 mg IV q 4 wk | Additional 16% ↑ in time to 1st on-study SRE (P = 0.0007) |
Notes:
a
n reflects patients in the 4 mg ZOL and placebo groups only;
b
percentage decrease in SRE risk and P value derived from the Cochrane database meta-analysis;25
c
n reflects patients in the 4 mg ZOL and 90 mg PAM groups only.
Abbreviations: BC, breast cancer; CLO, clodronate; Dmab, denosumab; IV, intravenous; MM, multiple myeloma; OST, other solid tumors; OS, overall survival; PAM, pamidronate; PFS, progression-free survival; PO, orally; q, every; SC, subcutaneously; SRE, skeletal-related event; ZOL, zoledronic acid; wk, week; vs, versus.