Background
Methods
Database and data collection
Study population
Variables
Statistical analysis
Results
Available TT agents and prescription patterns
Agent | Brand name | National insurance coverage year in Korea | Pathway | Dosing phase | Dosing therapy |
---|---|---|---|---|---|
Sunitinib | Sutene® | 2007 | TKI | First or more | P, S |
Sorafenib | Nexavar | 2007 | TKI | First or more | P, S |
Pazopanib | Votrient | 2011 | TKI | First or more | P, S |
Everolimus | Afinitor | 2011 | mTOR inhibitor | Second or more | S |
Axitinib | Inlyta | 2018 | TKI | Second | S |
Cabozantinib | Cabometyx | 2019 | TKI | Second or more | S |
Clinical characteristics of all patients according to the first- and second-line treatments
Variables | Total (n = 3,247) | First-line treatment | Second-line treatment | |||||
---|---|---|---|---|---|---|---|---|
SUN (1,787, 55.0%) | PAZ (1,460, 45.0%) | p | EVE (2,198, 67.7%) | AXI (773, 23.8%) | CAB (276, 8.5%) | p | ||
Age, mean (SD) | 61.27 (10.81) | 59.0 (10.05) | 64.05 (11.07) | < 0.0001 | 60.81 (10.77) | 62.61 (11.07) | 61.16 (10.17) | 0.0004 |
Age group | < 0.0001 | 0.0106 | ||||||
< 55 | 849 (26.2) | 562 (31.5) | 287 (19.7) | 610 (27.8) | 172 (22.3) | 67 (24.3) | ||
55–59 | 529 (16.3) | 338 (18.9) | 191 (13.1) | 357 (16.2) | 121 (15.7) | 51 (18.5) | ||
60–64 | 623 (19.2) | 380 (21.3) | 243 (16.6) | 406 (18.5) | 153 (19.8) | 64 (23.2) | ||
65–69 | 459 (14.1) | 222 (12.4) | 237 (16.2) | 316 (14.4) | 106 (13.7) | 37 (13.4) | ||
≥ 70 | 787 (24.2) | 285 (15.9) | 502 (34.4) | 509 (23.1) | 221 (28.5) | 57 (20.6) | ||
Sex (%) | < 0.0001 | 0.2816 | ||||||
Male | 2,534 (78.0) | 1,444 (80.8) | 1,090 (74.7) | 1,700 (77.3) | 610 (78.9) | 224 (81.2) | ||
Female | 713 (22.0) | 343 (19.2) | 370 (25.3) | 498 (22.7) | 163 (21.1) | 52 (18.8) | ||
Income level (%) | 0.3507 | 0.3291 | ||||||
0%–20% (lowest) | 616 (19.0) | 326 (18.2) | 290 (19.9) | 402 (18.3) | 155 (20.0) | 59 (21.3) | ||
20%–40% | 468 (14.4) | 264 (14.8) | 204 (14.0) | 318 (14.5) | 114 (14.8) | 36 (13.0) | ||
40%–60% | 550 (16.9) | 319 (17.9) | 231 (15.8) | 380 (17.3) | 121 (15.7) | 49 (17.8) | ||
60%–80% | 684 (21.1) | 381 (21.3) | 303 (20.8) | 451 (20.5) | 182 (23.5) | 51 (18.5) | ||
80%–100% | 929 (28.6) | 497 (27.8) | 432 (29.5) | 647 (29.4) | 201 (26.0) | 81 (29.4) | ||
Residence (%) | 0.1278 | 0.02 | ||||||
Metropolitan | 1,538 (47.4) | 868 (48.6) | 670 (45.9) | 1,066 (48.5) | 333 (43.1) | 139 (50.4) | ||
Other region | 1,709 (52.6) | 919 (51.4) | 790 (54.1) | 1,132 (51.5) | 440 (56.9) | 137 (49.6) | ||
CCI (%) | 0.0071 | 0.7865 | ||||||
0 | 1,056 (32.5) | 621 (34.8) | 435 (29.8) | 730 (33.2) | 237 (30.7) | 89 (32.3) | ||
1–2 | 1,643 (50.6) | 884 (49.4) | 759 (52.0) | 1,100 (50.1) | 403 (52.1) | 140 (50.7) | ||
≥ 3 | 548 (16.9) | 282 (15.8) | 266 (18.2) | 368 (16.7) | 133 (17.2) | 47 (17.0) | ||
Department (%) | 0.0016 | |||||||
Urology | 1,445 (44.5) | 941 (52.6) | 504 (34.5) | < 0.0001 | 1,021 (46.5) | 323 (41.8) | 101 (36.6) | |
Internal | 1,753 (54.0) | 825 (46.2) | 928 (63.6) | 1,145 (52.0) | 434 (56.1) | 174 (63.0) | ||
Others | 49 (1.5) | 21 (1.2) | 28 (1.9) | 32 (1.5) | 16 (2.1) | 1 (0.4) | ||
Time from initial diagnosis to systemic treatment | 0.8036 | 0.1589 | ||||||
< 1 year | 1,965 (60.5) | 1,078 (60.3) | 887 (60.7) | 1,355 (61.6) | 448 (58.0) | 162 (58.7) | ||
≥ 1 year | 1,282 (39.5) | 709 (39.7) | 573 (39.3) | 843 (38.4) | 325 (42.0) | 114 (41.3) |
Survival outcome of all patients according to the first- and second-line treatments and sequencing
Variables | Number (%) | HR | 95% CI | p | Median follow-up month (IQR) |
---|---|---|---|---|---|
Overall survival: first-line treatment | |||||
SUN | 1,787 (55.0) | Ref | 28 | ||
PAZ | 1,460 (45.0) | 1.209 | 1.113–1.315 | < 0.0001 | 21 |
Overall survival: second-line treatment | |||||
CAB | 276 (8.5) | Ref | 21 | ||
AXI | 773 (23.8) | 0.807 | 0.652–1.0 | 0.0495 | 24 |
EVE | 2,198 (67.7) | 1.658 | 1.377–1.997 | < 0.0001 | 26 |
Overall survival: sequencing | |||||
PAZ–AXI | 473 (14.6) | 1.088 | 0.798–1.484 | 0.5946 | 22 |
PAZ–CAB | 152 (4.7) | 1.383 | 0.960–1.991 | 0.0815 | 19.5 |
PAZ–EVE | 835 (25.7) | 2.423 | 1.823–3.219 | < 0.0001 | 21 |
SUN–AXI | 300 (9.2) | 0.795 | 0.569–1.110 | 0.1773 | 26 |
SUN–CAB | 124 (3.8) | Ref | 23 | ||
SUN–EVE | 1,363 (42.0) | 1.760 | 1.330–2.329 | < 0.0001 | 30 |
Clinical characteristics and survival outcomes of patients after PSM
Variables | Total (n = 2,428) | First-line treatment | Second-line treatment | |||||
---|---|---|---|---|---|---|---|---|
SUN (1,214, 50%) | PAZ (1,214, 50%) | p | EVE (1,614, 66.5%) | AXI (605, 24.9%) | CAB (209, 8.6%) | p | ||
Age, mean (SD) | 61.71 (10.52) | 61.43 (10.23) | 61.99 (10.8) | 0.1844 | 61.58 (10.47) | 62.11 (10.88) | 61.52 (9.84) | 0.5513 |
Age group | 1.0 | 0.1553 | ||||||
< 55 | 574 (23.6) | 287 (23.6) | 287 (23.6) | 388 (24.0) | 141 (23.3) | 45 (21.5) | ||
55–59 | 370 (15.3) | 185 (15.3) | 185 (15.3) | 243 (15.1) | 91 (15.0) | 36 (17.2) | ||
60–64 | 484 (19.9) | 242 (19.9) | 242 (19.9) | 302 (18.7) | 127 (21.0) | 55 (26.3) | ||
65–69 | 430 (17.7) | 215 (17.7) | 215 (17.7) | 302 (18.7) | 95 (15.7) | 33 (15.8) | ||
≥ 70 | 570 (23.5) | 285 (23.5) | 285 (23.5) | 379 (23.5) | 151 (25.0) | 40 (19.2) | ||
Sex (%) | 1.0 | 0.1443 | ||||||
Male | 1,864 (76.8) | 932 (76.8) | 932 (76.8) | 1,220 (75.6) | 477 (78.8) | 167 (79.9) | ||
Female | 564 (23.2) | 282 (23.2) | 282 (23.2) | 394 (24.4) | 128 (21.2) | 42 (20.1) | ||
Income level (%) | 0.3779 | 0.0653 | ||||||
0%–20% (lowest) | 485 (20.0) | 226 (18.6) | 259 (21.3) | 307 (19.0) | 126 (20.8) | 52 (24.9) | ||
20%–40% | 333 (13.7) | 161 (13.3) | 172 (14.2) | 228 (14.2) | 83 (13.7) | 22 (10.5) | ||
40%–60% | 419 (17.2) | 216 (17.8) | 203 (16.7) | 294 (18.2) | 90 (14.9) | 35 (16.8) | ||
60%–80% | 529 (21.8) | 266 (21.9) | 263 (21.7) | 338 (20.9) | 153 (25.3) | 38 (18.2) | ||
80%–100% | 662 (27.3) | 345 (28.4) | 317 (26.1) | 447 (27.7) | 153 (25.3) | 62 (29.6) | ||
Residence (%) | 0.0959 | 0.0224 | ||||||
metropolitan | 1,173 (48.3) | 607 (50) | 566 (46.6) | 807 (50) | 263 (43.5) | 103 (49.3) | ||
Other region | 1,255 (51.7) | 607 (50) | 648 (53.4) | 807 (50) | 342 (56.5) | 106 (50.7) | ||
CCI (%) | 1.0 | 0.9854 | ||||||
0 | 786 (32.4) | 393 (32.4) | 393 (32.4) | 528 (32.7) | 193 (31.9) | 65 (31.1) | ||
1–2 | 1,212 (49.9) | 606 (49.9) | 606 (49.9) | 800 (49.6) | 306 (50.6) | 106 (50.7) | ||
≥ 3 | 430 (17.7) | 215 (17.7) | 215 (17.7) | 286 (17.7) | 106 (17.5) | 38 (18.2) | ||
Department (%) | ||||||||
Urology | 1,060 (43.6) | 650 (53.5) | 410 (33.7) | < 0.0001 | 744 (46.1) | 246 (40.7) | 70 (33.5) | 0.0004 |
Internal | 1,330 (54.8) | 551 (45.4) | 779 (64.2) | 848 (52.5) | 344 (56.9) | 138 (66.0) | ||
Others | 38 (1.6) | 13 (1.1) | 25 (2.1) | 22 (1.4) | 15 (2.4) | 1 (0.5) | ||
Time from initial diagnosis to systemic treatment | 0.1467 | 0.2623 | ||||||
< 1 year | 1,463 (60.3) | 714 (58.8) | 749 (61.7) | 990 (61.3) | 355 (58.7) | 118 (56.5) | ||
≥ 1 year | 965 (39.7) | 500 (41.2) | 465 (38.3) | 624 (38.7) | 250 (41.3) | 91 (43.5) |
Variables | Number (%) | HR | 95% CI | p | Median follow-up month (IQR) |
---|---|---|---|---|---|
Overall survival: first-line treatment | |||||
SUN | 1,214 (50) | Ref | 29 | ||
PAZ | 1,214 (50) | 1.167 | 1.061–1.283 | 0.0015 | 21 |
Overall survival: second-line treatment | |||||
CAB | 209 (8.6) | Ref | 19 | ||
AXI | 605 (24.9) | 0.735 | 0.578–0.934 | 0.0118 | 24 |
EVE | 1,614 (66.5) | 1.544 | 1.253–1.903 | < 0.0001 | 25 |
Overall survival: sequencing | |||||
PAZ–AXI | 394 (16.2) | Ref | 23 | ||
PAZ–CAB | 131 (5.4) | 1.45 | 1.073–1.958 | 0.0155 | 18 |
PAZ–EVE | 689 (28.4) | 2.414 | 2.015–2.894 | < 0.0001 | 21 |
SUN–AXI | 211 (8.7) | 0.876 | 0.67–1.145 | 0.3312 | 26 |
SUN–CAB | 78 (3.2) | 1.089 | 0.749–1.582 | 0.655 | 23 |
SUN–EVE | 925 (38.1) | 1.769 | 1.482–2.111 | < 0.0001 | 31 |
Kaplan–Meier survival analysis of patients after PSM
Survival outcome of patients after PSM according to time from initial diagnosis to systemic treatment
A. Less than 1 year | ||||
Variables | Number (%) | HR | 95% CI | p |
Overall survival: first-line treatment | ||||
SUN | 714 (48.8) | Ref | ||
PAZ | 749 (51.2) | 1.172 | 1.042–1.319 | 0.0081 |
Overall survival: second-line treatment | ||||
CAB | 118 (8.1) | Ref | ||
AXI | 355 (24.3) | 0.764 | 0.573–1.020 | 0.0680 |
EVE | 990 (67.6) | 1.337 | 1.035–1.727 | 0.0261 |
Overall survival: sequencing | ||||
PAZ–AXI | 226 (15.5) | Ref | ||
PAZ–CAB | 73 (5.0) | 1.335 | 0.929–1.919 | 0.1187 |
PAZ–EVE | 450 (30.7) | 1.873 | 1.514–2.317 | < 0.0001 |
SUN–AXI | 129 (8.8) | 0.829 | 0.609–1.130 | 0.2352 |
SUN–CAB | 45 (3.1) | 1.057 | 0.674–1.658 | 0.8099 |
SUN–EVE | 540 (36.9) | 1.465 | 1.189–1.805 | 0.0003 |
B. Over than 1 year | ||||
Variables | Number (%) | HR | 95% CI | p |
Overall survival: first-line treatment | ||||
SUN | 500 (51.8) | Ref | ||
PAZ | 465 (48.2) | 1.120 | 0.951–1.317 | 0.1737 |
Overall survival: second-line treatment | ||||
CAB | 91 (9.4) | Ref | ||
AXI | 250 (25.9) | 0.610 | 0.394–0.944 | 0.0264 |
EVE | 624 (64.7) | 1.841 | 1.281–2.644 | 0.0010 |
Overall survival: sequencing | ||||
PAZ–AXI | 168 (17.4) | Ref | ||
PAZ–CAB | 58 (6.0) | 1.810 | 1.053–3.111 | 0.0318 |
PAZ–EVE | 239 (24.8) | 3.577 | 2.527–5.064 | < 0.0001 |
SUN–AXI | 82 (8.5) | 0.846 | 0.492–1.454 | 0.5446 |
SUN–CAB | 33 (3.4) | 1.207 | 0.616–2.364 | 0.5835 |
SUN–EVE | 385 (39.9) | 2.510 | 1.791–3.518 | < 0.0001 |