Table 4.
Biomarker levels at baseline and over time for patients receiving everolimus or placebo
| Baseline | Week 4 | Week 12 | Week 24 | Week 36 | Week 48 | ||
|---|---|---|---|---|---|---|---|
| VEGF‐A (pg ml −1 ) | |||||||
| Everolimus | Mean ± SD | 79.2 ± 69.8(n = 63) | 117.9 ± 137.3(n = 66) | 120.4 ± 85.9(n = 66) | 111.3 ± 76.5(n = 63) | 94.7 ± 54.5(n = 32) | 144.7 ± 89.8(n = 18) |
| Mean fold‐change (95% CI) | – | 1.51(1.33, 1.71)(n = 56) | 1.68(1.48, 1.91)(n = 56) | 1.59(1.39, 1.80)(n = 53) | 1.31(1.10, 1.56)(n = 26) | 1.79(1.45, 2.22)(n = 16) | |
| Placebo | Mean ± SD | 71.9 ± 49.7(n = 35) | 86.4 ± 73.8(n = 36) | 64.8 ± 45.8(n = 39) | 67.2 ± 42.3(n = 36) | 72.1 ± 45.3(n = 22) | 77.0 ± 55.1(n = 10) |
| Mean fold change (95% CI) | – | 1.10(0.92, 1.31)(n = 28) | 0.97(0.82, 1.16)(n = 29) | 1.04(0.88, 1.24)(n = 29) | 1.12(0.90, 1.38)(n = 18) | 0.90(0.66, 1.21)(n = 8) | |
| VEGF‐D (pg ml −1 ) | |||||||
|---|---|---|---|---|---|---|---|
| Everolimus | Mean ± SD | 2379.7 ± 2716.1(n = 73) | 1363.2 ± 1614.5(n = 74) | 795.6 ± 714.5(n = 72) | 762.8 ± 679.0(n = 72) | 707.2 ± 645.8(n = 60) | 674.5 ± 602.3(n = 35) |
| Mean fold‐change (95% CI) | – | 0.58(0.53, 0.64)(n = 69) | 0.38(0.35, 0.42)(n = 68) | 0.36(0.33, 0.40)(n = 67) | 0.34(0.31, 0.38)(n = 56) | 0.34(0.30, 0.38)(n = 33) | |
| Placebo | Mean ± SD | 2397.0 ± 2184.9(n = 35) | 2499.5 ± 2230.5(n = 37) | 2493.0 ± 2230.9(n = 38) | 2719.9 ± 2525.8(n = 35) | 2816.7 ± 2720.2(n = 32) | 2823.5 ± 2923.8(n = 19) |
| Mean fold‐change (95% CI) | – | 1.07(0.93, 1.22)(n = 33) | 1.05(0.92, 1.20)(n = 34) | 1.08(0.94, 1.23)(n = 32) | 1.09(0.95, 1.25)(n = 29) | 1.12(0.95, 1.32)(n = 16) | |
| sVEGFR1 (pg ml −1 ) | |||||||
|---|---|---|---|---|---|---|---|
| Everolimus | Mean ± SD | 98.8 ± 35.8(n = 63) | 106.6 ± 35.6(n = 66) | 107.0 ± 39.3(n = 66) | 101.1 ± 33.1(n = 63) | 101.1 ± 23.5(n = 32) | 108.6 ± 42.9(n = 18) |
| Mean fold‐change (95% CI) | – | 1.08(1.00, 1.16)(n = 59) | 1.05(0.98, 1.13)(n = 59) | 1.02(0.94 1.09)(n = 55) | 0.98(0.89, 1.08)(n = 28) | 0.98(0.87, 1.12)(n = 16) | |
| Placebo | Mean ± SD | 100.3 ± 27.1(n = 35) | 97.8 ± 32.3(n = 36) | 94.2 ± 28.3(n = 39) | 96.8 ± 23.0(n = 36) | 101.0 ± 23.6(n = 22) | 94.2 ± 34.5(n = 10) |
| Mean fold‐change (95% CI) | – | 0.93(0.85, 1.03)(n = 32) | 0.97(0.88, 1.07)(n = 35) | 0.98(0.89, 1.08)(n = 33) | 1.02(0.91, 1.15)(n = 19) | 1.03(0.87, 1.22)(n = 9) | |
| sVEGFR2 (pg ml −1 ) | |||||||
|---|---|---|---|---|---|---|---|
| Everolimus | Mean ± SD | 37918.2 ± 8015.3(n = 63) | 31437.6 ± 7296.3(n = 65) | 29633.1 ± 6440.4(n = 66) | 30779.7 ± 6038.1(n = 64) | 32472.6 ± 6637.1(n = 32) | 29808.1 ± 6997.9(n = 18) |
| Mean fold‐change (95% CI) | – | 0.83(0.73, 0.95)(n = 58) | 0.79(0.69, 0.89)(n = 59) | 0.81(0.72, 0.93)(n = 56) | 0.85(0.71, 1.02)(n = 28) | 0.79(0.62, 1.00)(n = 16) | |
| Placebo | Mean ± SD | 38219.5 ± 10697.6(n = 35) | 35383.8 ± 11169.0(n = 36) | 36729.3 ± 9633.7(n = 39) | 38213.1 ± 8503.9(n = 36) | 40973.8 ± 8023.8(n = 22) | 41663.6 ± 9975.1(n = 10) |
| Mean fold‐change (95% CI) | – | 0.70(0.59, 0.83)(n = 32) | 1.01(0.86, 1.19)(n = 35) | 1.01(0.86, 1.20)(n = 33) | 1.06(0.85, 1.32)(n = 19) | 1.07(0.78, 1.48)(n = 9) | |
| COL‐IV (μg l −1 ) | |||||||
|---|---|---|---|---|---|---|---|
| Everolimus | Mean ± SD | 285.1 ± 189.4(n = 75) | 165.2 ± 60.7(n = 74) | 144.4 ± 46.2(n = 75) | 137.9 ± 43.5(n = 73) | 137.5 ± 43.6(n = 63) | 137.8 ± 34.4(n = 36) |
| Mean fold‐change (95% CI) | – | 0.64(0.60, 0.67)(n = 71) | 0.56(0.53, 0.60)(n = 72) | 0.54(0.51, 0.57)(n = 70) | 0.53(0.50, 0.56)(n = 61) | 0.52(0.49, 0.52)(n = 34) | |
| Placebo | Mean ± SD | 320.9 ± 204.7(n = 36) | 299.3 ± 190.3(n = 38) | 315.4 ± 198.6(n = 39) | 329.4 ± 209.9(n = 36) | 326.4 ± 207.4(n = 33) | 327.2 ± 257.2(n = 20) |
| Mean fold‐change (95% CI) | – | 0.97(0.90, 1.05)(n = 35) | 1.01(0.93, 1.09)(n = 36) | 1.04(0.96, 1.13)(n = 34) | 1.03(0.96, 1.12)(n = 31) | 1.05(0.96, 1.14)(n = 18) | |
| c‐Kit (pg ml ‐1 ) | |||||||
|---|---|---|---|---|---|---|---|
| Everolimus | Mean ± SD | 100027.8 ± 27442.2(n = 63) | 105171.3 ± 28493.6(n = 65) | 100331.2 ± 25554.5(n = 66) | 100340.7 ± 26737.2(n = 64) | 101462.2 ± 25297.2(n = 32) | 100332.3 ± 21889.4(n = 18) |
| Mean fold‐change (95% CI) | – | 1.04(0.90, 1.20)(n = 58) | 1.00(0.87, 1.15)(n = 59) | 0.99(0.86, 1.15)(n = 56) | 1.02(0.83, 1.24)(n = 28) | 0.99(0.76, 1.29)(n = 16) | |
| Placebo | Mean ± SD | 103951.6 ± 30678.4(n = 35) | 93409.0 ± 32289.6(n = 36) | 96593.5 ± 27125.8(n = 39) | 99908.5 ± 22516.5(n = 36) | 106747.4 ± 22122.6(n = 22) | 91277.6 ± 14335.0(n = 10) |
| Mean fold‐change (95% CI) | – | 0.68(0.56, 0.82)(n = 32) | 1.03(0.86, 1.23)(n = 35) | 1.02(0.85, 1.23)(n = 33) | 1.07(0.84, 1.37)(n = 19) | 0.98(0.69, 1.39)(n = 9) | |
| PLGF (pg ml ‐1 ) | |||||||
|---|---|---|---|---|---|---|---|
| Everolimus | Mean ± SD | 11.8 ± 5.2(n = 63) | 11.1 ± 4.8(n = 66) | 12.5 ± 4.7(n = 66) | 12.1 ± 4.8(n = 63) | 12.8 ± 5.1(n = 32) | 13.9 ± 5.5(n = 18) |
| Mean fold‐change (95% CI) | – | 0.90(0.81, 0.99)(n = 55) | 1.05(0.95, 1.16)(n = 56) | 1.04(0.94 1.16)(n = 52) | 0.98(0.86, 1.12)(n = 28) | 1.03(0.87, 1.23)(n = 16) | |
| Placebo | Mean ± SD | 12.2 ± 4.0(n = 35) | 11.6 ± 4.3(n = 36) | 12.0 ± 3.9(n = 39) | 13.2 ± 4.2(n = 36) | 12.3 ± 3.7(n = 22) | 12.4 ± 3.4(n = 10) |
| Mean fold‐change (95% CI) | – | 0.92(0.81, 1.05)(n = 32) | 1.04(0.91, 1.18)(n = 34) | 1.07(0.94, 1.22)(n = 33) | 1.05(0.89, 1.23)(n = 19) | 1.05(0.83, 1.33)(n = 9) | |
COL‐IV, collagen type IV; PLGF, placental growth factor; VEGF‐A, vascular endothelial growth factor A; VEGF‐D, vascular endothelial growth factor D; sVEGFR1, soluble VEGF receptor 1; sVEGFR2, soluble VEGF receptor 2.