Table 3.
Potential predictive biomarkers of benefit of antiangiogenic therapy
| Cancer type (and study phase) |
Treatment | Study size and time points |
Biomarker findings | Comments and references | |
|---|---|---|---|---|---|
| Antiangiogenic agent |
Cytotoxic agent |
||||
| mNSCLC (II–III) | Bevacizumab | Carboplatin and paclitaxel |
n = 56–166 Pre and post (week 7) |
Baseline sICAM1 is an independent prognostic factor for OS |
Biomarker not specific for bevacizumab41 |
| mBC (III) | Bevacizumab | Paclitaxel |
n = 363 Baseline |
VEGF-2578 AA genotype: superior median OS VEGF-1154 A allele: superior median OS Patients with grade 3/4 hypertension: superior median OS VEGF=634 CC and VEGF-1498 TT genotypes: significantly less grade 3/4 hypertension |
Needs independent validation studies38 |
| mBC (chemorefractory) (II) |
Bevacizumab | Vinorelbine |
n = 56 Baseline |
Lower baseline levels of plasma VEGF were associated with longer TTP |
Not clear if these are prognostic or predictive biomarker candidate on the basis of single-arm study39 |
| Advanced RCC (bevacizumab refractory) (II) |
Sunitinib | No |
n = 61 Pre and post (day 28) |
Lower baseline levels of plasma sVEGFR3 and VEGF-C were associated with longer PFS |
Not clear if these are prognostic or predictive biomarkers on the basis of single-arm study48 |
| mRCC (II) | Vatalanib | No |
n = 10 Pre and post (1 month) |
Patients with stable disease or partial response had a significant decrease in tumor blood flow at 1 month |
Not clear if these are prognostic or predictive biomarkers on the basis of single-arm study81 |
| Advanced HCC (II) | Sunitinib | No |
n = 34 Pre and post (days 14,28, 56, 84 and 112) |
Patients with clinical benefit had significantly greater decreases in Ktrans, IL-6 and soluble c-KIT at day 14 An increase in AFP, soluble c-KIT, SDF1α, sVEGFR1, CPCs or IL-6 at any time-point was associated with rapid progression and/or death |
Not clear if these are prognostic or predictive biomarkers on the basis of single-arm study23 |
| Advanced ovarian cancer (II) |
Bevacizumab | Low-dose carboplatin |
n = 53 Baseline |
IL-8 A-251T polymorphism might be a molecular predictor of response to bevacizumab-based chemotherapy |
Not clear if these are prognostic or predictive biomarkers on the basis of single-arm study62 |
| mCRC (III) | Vatalanib | FOLFOX |
n = 254 (sera) n = 191 (tissue biopsy) Baseline |
Patients with high baseline serum LDH in the vatalanib treatment arm had significantly longer PFS and OS Responses to vatalanib and chemotherapy correlated directly with tissue mRNA levels of VEGFR1, LDHA and Glut1 (in previously untreated patients [CONFIRM1]) and inversely with HIF-1α in the second-line setting (CONFIRM2) |
Both trials failed to meet the prespecified end point and the development of the drug in mCRC was discontinued60,61 |
| NSCLC (II) | Vandetanib | Gemcitabine Docetaxel Paclitaxel and carboplatin |
n = 207 Baseline |
Low baseline VEGF: lower risk of progressive disease when treated with vandetanib vs gefitinib Low baseline VEGF: lower risk of progressive disease when treated with vandetanib and docetaxel vs docetaxel monotherapy |
Not clear if VEGF is a prognostic or a predictive biomarker given the poor anti-VEGFR activity of the agent46 |
| rGBM (II) | Bevacizumab | Irinotecan |
n = 21 Pre and post (week 1/2, 6) |
Both early and later FLT-PET changes: more significant predictors of OS compared with the MRI changes |
The uptake of fluorothymidine by a tumor might be confounded by changes in vascular permeability induced by bevacizumab70 |
| rGBM (II) | Cediranib | No |
n = 31 Pre and post (days 1, 2, 9, 28, 56, 84 and 112) |
Patients with clinical benefit had significantly greater decreases in Ktrans, collagen IV and CECs at day 2 Progression was associated with an increase in SDF1α and bFGF |
Not clear if these are prognostic or predictive biomarker candidate on the basis of single-arm study37 |
Abbreviations: AFP, alphafetoprotein; bFGF, basic fibroblast growth factor; CECs, circulating endothelial cells; CPC, circulating progenitor cell; FLT-PET, fluorothymidine PET; FOLFOX, 5-FU, leucovorin and oxaliplatin; HCC hepatocellular carcinoma; HIF-1α, hypoxia inducible factor 1α; IL, interleukin; LDH, lactate dehydrogenase; mBC, metastatic breast cancer; mCRC, metastatic colorectal cancer; mNSCLC, metastatic non-small-cell lung cancer; OS, overall survival; PFS, progression-free survival; RCC, renal cell carcinoma; rGBM, recurrent glioblastoma; sICAM1, soluble intercellular adhesion molecule 1; SDF1α, stromal derived factor 1 alpha; TTP, time-to-progression.