Table 4.
Univariate and multivariate analyses of progression-free survival and overall survival by treatment arm using the Cox proportional hazards model
| Variables [n for each group] | PFS | OS | ||
|---|---|---|---|---|
| HR (95 % CI) | Wald P | HR (95 % CI) | Wald P | |
| Sunitinib | ||||
| Univariate analysis | ||||
| Age (<65 vs ≥65 years) [17, 16] | 0.595 (0.179–1.99) | 0.3990 | 0.698 (0.228–2.14) | 0.5290 |
| Sex (M vs F) [21, 12] | 0.893 (0.267–2.99) | 0.8540 | 0.779 (0.24–2.53) | 0.6780 |
| No. of disease sites (<3 vs ≥3) [18, 15] | 1.16 (0.383–3.47) | 0.7950 | 2.12 (0.694–6.51) | 0.1870 |
| ECOG performance status (0 vs 1) [25, 8] | 1.58 (0.474–5.26) | 0.4540 | 2.37 (0.773–7.25) | 0.1310 |
| Nephrectomy (no vs yes) [4, 29] | 0.269 (0.071–1.02) | 0.0531 | 0.197 (0.053–0.729) | 0.0150 |
| Time since diagnosis (<1 vs ≥1 year) [21, 12] | 0.301 (0.066–1.37) | 0.1210 | 0.274 (0.061–1.24) | 0.0921 |
| Risk factors based on published MSKCC dataa (0 vs 1 or 2) [11, 22] | 2.74 (0.599–12.5) | 0.1940 | 6.84 (0.888–52.6) | 0.0649 |
| Baseline VEGF-A (ng/10 mL) [33] | 1.28 (1.06–1.55) | 0.0108 | 1.33 (1.09–1.63) | 0.0052 |
| Baseline VEGF-C (ng/mL) [33] | 6.42 (1.25–33) | 0.0259 | 2.91 (0.703–12.1) | 0.1410 |
| Baseline sVEGFR-3 (ng/mL) [33] | 1.04 (1.01–1.06) | 0.0026 | 1.04 (1.02–1.07) | 0.0012 |
| Baseline IL-8 (pg/mL) [31] | 1.05 (0.991–1.11) | 0.1010 | 1.08 (1.03–1.14) | 0.0026 |
| Multivariate analysis | ||||
| Nephrectomy (no vs yes) [4, 29] | – | – | 0.385 (0.065–2.28) | 0.290 |
| Baseline VEGF-A (ng/10 mL) [33] | 1.05 (0.677–1.63) | 0.82 | 0.559 (0.310–1.01) | 0.053 |
| Baseline VEGF-C (ng/mL) [33] | 4.84 (0.665–35.23) | 0.12 | – | – |
| Baseline sVEGFR-3 (ng/mL) [33] | 1.03 (0.975–1.09) | 0.300 | 1.064 (1.004–1.13) | 0.037 |
| Baseline IL-8 (pg/mL) [31] | – | – | 1.110 (1.022–1.20) | 0.013 |
| Interferon-alpha | ||||
| Univariate analysis | ||||
| Age (<65 vs ≥65 years) [16, 14] | 3.87 (0.967–15.5) | 0.0558 | 1.21 (0.454–3.23) | 0.7040 |
| Sex (M vs F) [24, 6] | 1.36 (0.347–6.89) | 0.7220 | 1.92 (0.612–6.02) | 0.2640 |
| No. of disease sites (<3 vs ≥3) [17, 13] | 1.16 (0.408–3.31) | 0.7780 | 3.78 (1.39–10.3) | 0.0092 |
| ECOG performance status (0 vs 1) [20, 10] | 1.88 (0.656–1.39) | 0.2400 | 2.05 (0.735–5.7) | 0.1700 |
| Nephrectomy (no vs yes) [3, 27] | 0.06 (0.008–0.418) | 0.0049 | 0.09 (0.018–0.478) | 0.0044 |
| Time since diagnosis (<1 vs ≥1 year) [14, 16] | 1.18 (0.404–3.44) | 0.7630 | 0.68 (0.252–1.83) | 0.4450 |
| Risk factors based on published MSKCC dataa (0 vs 1 or 2) [12, 17] | 0.77 (0.268–2.22) | 0.6310 | 1.99 (0.631–6.27) | 0.2410 |
| Baseline VEGF-A (ng/10 mL) [30] | 3.05 (0.48–19.4) | 0.237 | 1.24 (1.04–1.47) | 0.0174 |
| Baseline VEGF-C (ng/mL) [30] | 3.64 (1.22–10.9) | 0.0206 | 2.12 (0.917–4.89) | 0.0790 |
| Baseline sVEGFR-3 (ng/mL) [30] | 1.01 (0.971–1.06) | 0.5270 | 1.04 (1–1.08) | 0.0505 |
| Baseline IL-8 (pg/mL) [29] | 1.04 (1–1.07) | 0.0423 | 1.02 (1–1.03) | 0.0094 |
| Multivariate analysis | ||||
| No. of disease sites (<3 vs ≥3) [17, 13] | – | – | 2.428 (0.752–7.84) | 0.140 |
| Nephrectomy (no vs yes) [3, 27] | 0.113 (0.008–1.52) | 0.100 | 0.218 (0.028–1.67) | 0.140 |
| Baseline VEGF-A (ng/10 mL) [30] | – | – | 0.925 (0.525–1.63) | 0.790 |
| Baseline VEGF-C (ng/mL) [30] | 1.470 (0.158–13.6) | 0.740 | – | – |
| Baseline IL-8 (pg/mL) [29] | 1.018 (0.964–1.08) | 0.520 | 1.013 (0.969–1.06) | 0.560 |
For binary variables, a hazard ratio <1 represents risk reduction for the first category and a hazard ratio >1 represents risk reduction for the second category; for continuous variables (i.e., the soluble proteins), a hazard ratio >1 equates to risk reduction when the value decreases and a hazard ratio <1 equates to risk reduction when the value increases
Variables that were significant (P < 0.05) by univariate analysis were evaluated in the multivariate model
CI confidence interval, ECOG Eastern Cooperative Oncology Group, HR hazard ratio, MSKCC Memorial Sloan-Kettering Cancer Center, PFS progression-free survival, OS overall survival
aIncludes low serum hemoglobin level; elevated corrected serum calcium level; elevated serum lactate dehydrogenase level; poor performance status; and interval of <1 year between diagnosis and treatment [8]