Table 3.
Risk factor table for treatment-related death or death during trial
| Treatment-related death | Death during protocol treatment | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| N (%) | Number toxicities (%) | RR | 95%CI | p-value | Number events (%) | RR | 95%CI | p-value | ||
| Age | ||||||||||
| Continuous (with 1 increase) | 1.02 | (1.01–1.04) | 0.006 | 1.01 | (1.00–1.01) | 0.009 | ||||
| < 18 | 1169 (8.4) | 3 (0.3) | 0.45 | (0.15, 1.40) | 0.169 | 85 (7.3) | 0.95 | (0.69, 1.30) | 0.739 | |
| 18–59 | 6899 (49.8) | 39 (0.6) | Ref | 528 (7.7) | Ref | |||||
| ≥ 60 | 5778 (41.7) | 51 (0.9) | 1.58 | (1.02, 2.41) | 0.041 | 498 (8.6) | 1.13 | (1.00, 1.27) | 0.050 | |
| Sex | ||||||||||
| Female | 7531 (54.4) | 47 (0.6) | Ref | 529 (7.0) | Ref | |||||
| Male | 6316 (45.6) | 46 (0.7) | 1.21 | (0.80, 1.83) | 0.370 | 582 (9.2) | 1.17 | (1.03, 1.33) | 0.370 | |
| PS | ||||||||||
| 0–1 | 6460 (94.1) | 43 (0.7) | Ref | 482 (7.5) | Ref | |||||
| ≥2 | 404 (5.9) | 7 (1.7) | 2.62 | (1.24, 5.54) | 0.011 | 110 (27.3) | 3.16 | (2.52, 3.97) | <0.001 | |
| BMI | ||||||||||
| Continuous | 1.01 | (0.97, 1.06) | 0.554 | 0.97 | (0.95, 0.98) | <0.001 | ||||
| <18.5 | 257 (3.7) | 1 (0.4) | 0.56 | (0.08, 3.80) | 0.556 | 36 (14.0) | 1.41 | (1.00, 1.98) | 0.052 | |
| 18.5–25 | 2489 (35.6) | 18 (0.7) | Ref | 257 (10.3) | Ref | |||||
| 25–30 | 2395 (34.2) | 15 (0.6) | 0.88 | (0.46, 1.67) | 0.688 | 196 (8.2) | 0.84 | (0.68, 1.04) | 0.104 | |
| ≥ 30 | 1858 (26.5) | 16 (0.9) | 1.18 | (0.57, 2.44) | 0.652 | 115 (6.2) | 0.62 | (0.50, 0.78) | <0.001 | |
| Albumin | ||||||||||
| Continuous | 0.47 | (0.30, 0.72) | 0.001 | 0.32 | (0.29, 0.37) | < 0.001 | ||||
| ≥ 3.5 g/dL | 3856 (68.7) | 20 (0.5) | Ref | 190 (4.9) | Ref | |||||
| < 3.5 g/dL | 1757 (31.3) | 23 (1.3) | 2.62 | (1.51, 4.54) | <0.001 | 300 (17.1) | 3.38 | (2.80, 4.08) | < 0.001 | |
| Hemoglobin | ||||||||||
| Continuous | 1.01 | (0.84, 1.21) | 0.925 | 0.79 | (0.75, 0.83) | < 0.001 | ||||
| ≥ 12.0 g/dL | 3513 (52.3) | 22 (0.6) | Ref | 185 (5.3) | Ref | |||||
| < 12.0 g/dL | 3209 (47.7) | 27 (0.8) | 1.32 | (0.79, 2.20) | 0.288 | 395 (12.3) | 2.15 | (1.76, 2.64) | < 0.001 | |
| Study Activation Year | ||||||||||
| 2000–2005 | 5882 (42.5) | 44 (0.7) | Ref | 327 (5.6) | Ref | |||||
| 2006–2012 | 6220 (44.9) | 37 (0.6) | 0.76 | (0.48, 1.21) | 0.249 | 614 (9.9) | 1.49 | (1.13, 1.98) | 0.005 | |
| 2013–2019 | 1745 (12.6) | 12 (0.7) | 0.94 | (0.47, 1.82) | 0.830 | 170 (9.7) | 1.65 | (1.15, 2.36) | 0.006 | |
| Investigational Agent | ||||||||||
| Antiangiogenesis | 2689 (19.4) | 32 (1.2) | 2.19 | (1.41, 3.39) | <0.001 | 224 (8.3) | 1.06 | (0.77, 1.47) | 0.725 | |
| Checkpoint inhibitor | 817 (5.9) | 5 (0.6) | 0.95 | (0.41, 2.21) | 0.909 | 70 (8.6) | 1.12 | (0.66, 1.90) | 0.681 | |
| Chemotherapy | 6981 (50.4) | 48 (0.7) | 1.03 | (0.66, 1.59) | 0.912 | 432 (6.2) | 0.68 | (0.52, 0.89) | 0.005 | |
| Cytokine | 367 (2.7) | 1 (0.3) | 0.39 | (0.06, 2.50) | 0.320 | 12 (3.3) | 0.49 | (0.26, 0.90) | 0.021 | |
| DNA repair | 1791 (12.9) | 12 (0.7) | 0.91 | (0.47, 1.79) | 0.790 | 152 (8.5) | 1.17 | (0.76, 1.80) | 0.480 | |
| Epigenetic modulation | 1255 (9.1) | 7 (0.6) | 0.82 | (0.41, 1.66) | 0.582 | 139 (11.1) | 1.34 | (0.92, 1.94) | 0.129 | |
| Gene/cellular therapy | 132 (1.0) | 0 (0.0) | NA | NA | NA | 8 (6.1) | 1.00 | (0.29, 3.49) | 1.000 | |
| Monoclonal antibody | 468 (3.4) | 2 (0.4) | 0.66 | (0.16, 2.71) | 0.562 | 25 (5.3) | 0.56 | (0.34, 0.93) | 0.024 | |
| Protein metabolism | 1126 (8.1) | 16 (1.4) | 2.39 | (1.41, 4.06) | 0.001 | 81 (7.2) | 0.94 | (0.66, 1.33) | 0.731 | |
| Receptor/signal transduction pathway | 4029 (29.1) | |||||||||
| agent | 18 (0.4) | 0.60 | (0.36, 1.00) | 0.051 | 362 (9.0) | 1.21 | (0.95, 1.54) | 0.128 | ||
| Vaccine | 773 (5.6) | 1 (0.1) | 0.19 | (0.03, 1.29) | 0.089 | 46 (6.0) | 0.93 | (0.46, 1.88) | 0.847 | |
| Others | 2953 (21.3) | 22 (0.7) | 1.17 | (0.69, 1.96) | 0.559 | 210 (7.1) | 1.00 | (0.72, 1.39) | 0.992 | |
| Combination Therapy | ||||||||||
| Monotherapy | 4108 (29.7) | 28 (0.7) | Ref | 391 (9.5) | Ref | 0.685 | ||||
| Combination Therapy | 9739 (70.3) | 65 (0.7) | 0.99 | (0.61, 1.60) | 0.958 | 720 (7.4) | 0.95 | (0.72, 1.24) | ||
| Trial type | ||||||||||
| Solid tumor focused trial | 12179 (88.0) | 85 (0.7) | Ref | 923 (7.6) | Ref | |||||
| All-comer trial | 1668 (12.0) | 8 (0.5) | 0.70 | (0.33, 1.52) | 0.371 | 188 (11.3) | 1.48 | (1.10, 1.97) | 0.008 | |
Abbreviations: RR, risk ratio; CI, confidence interval; PS, performance status; BMI, body mass index; p-values are obtained using Wald test