2.
Studies assessing serological biomarkers in relation to activity or efficacy of BEV
| Author | Trial | Cancer | n/N* | Assessment | Finding |
| BEV, bevacizumab; Doc, docetaxel; PTX, paclitaxel; Tras, trastuzumab; NVB, vinorelbine; CTX, cyclophosphamide; MBC, metastatic breast cancer; LABC, locally advanced breast cancer; TNBC, triple negative breast cancer; VEGF, vascular endothelial growth factor; pVEGF-A, plasma VEGF-A; EGFR, epidermal growth factor receptor; sVEGFR, soluble vascular endothelial growth factor receptor; ICAM-1, intracellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule 1; MMP, matrix metalloproteinases; Ang II, angiopoietin-2; sTie2, receptor tyrosine kinases 2; PlGF, placental growth factor; bFGF, basic fibroblast growth factor; IL, interleukin; TNF-α, tumor necrosis factor alpha; SDF1α, stromal cell-derived factor α; CAIX, carbonic anhydrase 9; IGF-1, insulin-like growth factor 1; CCL, chemokine (C-C motif) ligand; DFS, disease-free survival; OS, overall survival; PFS, progression-free survival; TTP, time to treatment failure; *, Number of patients in sub study/parent trial. | |||||
| Miles et al. (9) | AVADO: phase III, Doc vs. Doc + BEV 7.5 mg/kg or 15 mg/kg | First line MBC | 396/736 | VEGF-A, EGFR-1, VEGFR-2, E-selectin, ICAM-1, VCAM-1 | PVEGF-A and VEGFR-2 are potential predictive markers for BEV efficacy |
| Baar et al. (25) | Randomized, phase II, Doc vs. Doc + BEV | Neoadjuvant LABC | 49/49 | VEGF, VCAM-1, ICAM-1, E-selectin | Baseline VCAM-1 and E-selectin associated with tumor regression |
| Miles et al. (42) | MERiDiAN: prospective phase III, PTX + BEV vs. PTX + placebo | First line HER2 negative MBC | 481/481 | VEGF-A | Baseline pVEGF-A level has no predictive effect for BEV treatment |
| Tabouret et al. (43) | BEVERLY-2: single arm, phase II, Tras based chemotherapy vs. Trast based chemotherapy + BEV | Neoadjuvant and adjuvant breast cancer | 45/52 | MMP2, MMP9 | High MMP2 and low MMP9 level were associated with better DFS and OS |
| Gianni et al. (44) | AVEREL: phase III, Doc + Tras vs. Doc + Tras + BEV | First line LABC/MBC | 162/424 | VEGF-A | High baseline pVEGF-A was associated with poorer outcome and BEV improved PFS in this subgroup |
| Cameron et al. (45) | Beatrice: anthracycline and/or Taxane vs. anthracycline and/or Taxane + BEV | Adjuvant TNBC | 1,155/2,591 | VEGF-A, VEGFR-2 | Neither prognostic nor predictive value with baseline pVEGF-A, no prognostic but potential predictive value for BEV efficacy with baseline plasma VEGFR-2 |
| Burstein et al. (46) | Single arm, phase II, NVB + BEV | Refractory MBC | 49/56 | VEGF | Lower levels of baseline VEGF were associated with longer TTP |
| Tolaney et al. (47) | Phase II, single arm, BEV followed by dose-dense doxorubicin + CTX + PTX | Neoadjuvant breast cancer | 103/104 | VEGF, sVEGFR-1, sVEGFR-2, Ang II, sTie2, PlGF, bFGF, IL-1β, IL-6, IL-8, TNF-α, SDF1α, CAIX, IGF-1 | High VEGF levels at baseline and low sVEGFR1 and PLGF levels before combination treatment were associated with pathologic response |
| Cattin et al. (48) | Healthy control, pilot study, PTX vs. PTX + BEV | First line MBC | 21 patients, 12 healthy donors | TNF-α, IL-12p70, IL-10, CCL20, CCL2 | BEV significantly decreased IL-10 level |