Table 2.
Trials demonstrating anticancer benefits of bisphosphonates
| Study (follow-up) | N | Tumor type | BP | Results |
|---|---|---|---|---|
| Neoadjuvant setting | ||||
| Neoadjuvant AZURE34 (6 mo) | 205 | BC | ZOL 4 mg IV q 3–4 wk for 6 doses | ↓ RITS by 44% (27.4 mm vs 15.5 mm; P = 0.006) ↑ pCR rate by nearly 2-fold (P = 0.146) |
| Adjuvant setting | ||||
| Powles et al35 (5.6 y) | 1069 | BC | CLO 1600 mg/d for 2 y | ↑ BMFS (HR = 0.692; P = 0.043) ↑ OS (HR = 0.768; P = 0.048) |
| Diel et al36 (36 mo) (8.5 y)37 | 302 | BC | CLO 1600 mg/d for 2 y | ↑ BMFS (92% vs 83%; P = 0.003) ↑ OS (HR = 96% vs 85%; P = 0.0001) ↑ OS (79.6% vs 59.3%; P = 0.049) |
| Saarto et al (5 y)38 (10 y)39 | 299 | BC | CLO 1600 mg/day for 3 y | ↓ OS (70% vs 83%; P = 0.009) ↓ DFS (56% vs 71%; P = 0.007) ↓ DFS (45% vs 58%; P = 0.01); Similar OS |
| NSABP-3440 (8.4 y) | 3323 | BC | CLO 1600 mg/d for 3 yr | No effect on DFS (HR = 0.91; P = 0.27) ↑ BMFI (HR = 0.63; P = 0.024) and ↑ NBMFI (HR = 0.63; P = 0.015) in women ≥ 50 y |
| GAIN41 (39 mo) | 3023 | BC | IBN 50 mg/d for 2 y | No effect on DFS (HR = 0.945; P = 0.59) or OS (HR = 1.04; P = 0.80) |
| Lin et al42 (24 mo) | 45 | BC | ZOL 4 mg IV monthly for 2 y | ↓ In persistent DTCs: ↓ In 66% of patients at 1 y (P = 0.0018) ↓ In 71% of patients at 2 y (P = 0.01) |
| Solomayer et al43 (12 mo) | 76 | BC | ZOL 4 mg IV q 4 wk for 2 y | ↓ In persistent DTCs (P = 0.066) ↑ DTC-free patients (67% vs 35%; P = 0.009) |
| Aft et al44 (3 mo) | 120 | BC | ZOL 4 mg IV q 3 wk for 1 y | ↓ In persistent DTCs (30% vs 47%; P = 0.054) |
| Rack et al45 (39 mo) | 172 | BC | ZOL 4 mg IV q 4 wk for 6 mo | ↓ Proportion with persistent DTCs after ZOL (13% vs 27%; P = 0.099) |
| ZO-FAST (36 mo)46 (60 mo)47 | 1065 | BCa | ZOL 4 mg IV q 6 mo for 5 y; immediate vs delayed | ↑ DFS (HR = 0.588; P = 0.0314) with immediate vs delayed ZOL ↑ DFS (HR = 0.66; P = 0.0375) |
| ABCSG-12 (48 mo)48 (84 mo)49 | 1803 | BCb | ZOL 4 mg IV q 6 mo for 3 y |
↑ DFS (HR = 0.64; P = 0.01) ↑ DFS (HR = 0.72; P = 0.014) ↑ OS (HR = 0.63; P = 0.049) |
| AZURE (59 mo)50 | 3360 | BC | ZOL 4 mg IV q 3–4 wk × 6; 4 mg q 3 mo × 8; 4 mg q 6 mo × 5 |
No change in DFS in overall population (HR = 0.98; P = 0.79) Trend ↑ OS in the overall population (HR = 0.85; P = 0.07) ↑ IDFS (HR = 0.75; P = 0.02) and ↑ OS (HR = 0.74; P = 0.04) in women > 5 y postmenopause (n = 1041) |
| Metastatic setting | ||||
| Mystakidou et al51 (18 mo) | 40 | Advanced solid tumors (no BM) | ZOL 4 mg IV monthly | ↑ BMFS at 12 mo (60% vs 10%; P < 0.0005) ↑ BMFS at 18 mo (20% vs 5%; P = 0.0002) |
| Zaghloul et al52 (24 wk) | 40 | Bladder cancer | ZOL 4 mg IV monthly for 6 mo | ↑ 1-y OS (36.3% vs 0%; P = 0.004) |
| Zarogoulidis et al53 | 144 | LC | ZOL 4 mg IV q 21 d | ↑ OS by > 6 mo (578 d vs 384 d; P < 0.001) |
| Aviles et al54 (49.6 mo) | 94 | MM | ZOL 4 mg IV q 28 d | ↑ 5-y OS (80% vs 46%; P < 0.01) ↑ 5-y EFS (80% vs 52%; P < 0.01) |
| MRC Myeloma IX24 (3.7 y) | 1960 | MM | ZOL 4 mg IV q 3–4 wk | ↑ PFS (HR = 0.883; P = 0.0179) ↑ OS (HR = 0.842; P = 0.0118) |
Notes:
Postmenopausal women with early-stage endocrine-responsive breast cancer;
premenopausal women with early stage endocrine-responsive BC. Hamilton E, Clay TM, Blackwell KL. New perspectives on zoledronic acid in breast cancer: potential augmentation of anticancer immune response. Cancer Invest. 2011;29(8):533–541. Copyright 2011, Informa Healthcare. Reproduced with permission of Informa Healthcare.55
Abbreviations: BC, breast cancer; BMFI, bone metastasis-free interval; BMFS, bone metastasis-free survival; DFS, disease-free survival; DTC, disseminated tumor cell; EFS, event-free survival; HR, hazard ratio; IBN, ibandronate; I IDFS, invasive disease-free survival; IV, intravenous; LC, lung cancer; MM, multiple myeloma; NBMFI, nonbone metastasis-free interval; OS, overall survival; pCR, pathologic complete response; PFS, progression-free survival; q, every; RITS, residual invasive tumor size; ZOL, zoledronic acid.