Table 2.
Associations between maximal percent changes in biomarker concentrations or baseline biomarker concentrations and efficacy endpoints
| Biomarker | Median value (range) | Endpoint |
< Median value |
≥ Median value |
HR* (95% CI) | p | ||
|---|---|---|---|---|---|---|---|---|
| n | Median time to event, weeks | n | Median time to event, weeks | |||||
|
Median maximal percent change in biomarker concentration from C1D1 to C2D28 | ||||||||
| sKIT |
48.6% (−) |
TTP |
30 |
7.9 |
31 |
21.7 |
5.99 (3.06-11.7) |
< 0.0001 |
| |
|
OS |
|
25.7 |
|
53.7 |
2.33 (1.16-4.70) |
0.018 |
| VEGF-A |
89.4% (−) |
TTP |
30 |
9.9 |
31 |
10.3 |
1.75 (0.99-3.09) |
0.054 |
| |
|
OS |
|
32.3 |
|
62.6 |
2.12 (1.06-4.23) |
0.032 |
| sVEGFR-2 |
55.8% (−) |
TTP |
30 |
10.1 |
31 |
10.2 |
1.07 (0.62-1.85) |
0.81 |
| |
|
OS |
|
36.0 |
|
53.7 |
1.52 (0.76-3.02) |
0.24 |
| sVEGFR-3 |
52.8% (−) |
TTP |
27 |
10.1 |
28 |
11.0 |
1.40 (0.77-2.52) |
0.27 |
| |
|
OS |
|
51.6 |
|
52.7 |
1.98 (0.79-4.96) |
0.15 |
|
Median baseline biomarker concentration | ||||||||
| sKIT |
70 ng/mL (26–113) |
TTP |
28 |
10.6 |
28 |
10.1 |
1.08 (0.60-1.96) |
0.80 |
| |
|
OS |
|
37.4 |
|
45.1 |
1.13 (0.55-2.35) |
0.74 |
| VEGF-A |
53 pg/mL (14–709) |
TTP |
25 |
10.1 |
26 |
10.2 |
0.71 (0.38-1.33) |
0.29 |
| |
|
OS |
|
Not reached |
|
33.0 |
0.55 (0.25-1.22) |
0.14 |
| sVEGFR-2 |
11 ng/mL (4–15) |
TTP |
28 |
10.3 |
28 |
10.1 |
0.98 (0.54-1.76) |
0.94 |
| |
|
OS |
|
37.4 |
|
62.6 |
1.19 (0.57-2.46) |
0.65 |
| sVEGFR-3 |
68 ng/mL (25–152) |
TTP |
28 |
10.1 |
28 |
10.2 |
0.97 (0.54-1.75) |
0.93 |
| OS | 37.4 | 53.7 | 1.43 (0.68-2.98) | 0.35 | ||||
C, cycle; CI, confidence interval; D, day; HR, hazard ratio; OS, overall survival; sKIT, soluble KIT; sVEGFR, soluble vascular endothelial growth factor receptor; TTP, time to tumor progression; VEGF, vascular endothelial growth factor.
*HR > 1 favors the groups with values ≥ median value.