1Division of Hematology/Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
3Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Seoul, Korea
Copyright © 2021 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
single (fluoropyrimidine [F], taxane [T] or irinotecan [I]);
doublet (F/platinum [P], T/P, F/I, F/T, T/I, anthracycline [A]/P, or A/F);
doublet/Tmab (F/P with trastuzumab);
doublet/novel (F/P with novel agents in clinical trials);
triplet (F/P/T);
single/Rmab (T with ramucirumab);
immunotherapy (immune checkpoint inhibitors).
Ethical Statement
This study protocol was approved by the Institutional Review Board of the Asan Medical Center, and informed consent was waived because of the retrospective nature of the study.
Author Contributions
Conceived and designed the analysis: Kang YK, Ryu MH, Koo DH.
Collected the data: Kang YK, Ryu MH, Chae H, Kim EJ, Moon MS.
Contributed data or analysis tools: Koo DH, Lee MY, Kang YK, Ryu MH, Chae H, Kim EJ, Moon MS.
Performed the analysis: Koo DH, Lee MY, Kang YK, Ryu MH.
Wrote the paper: Koo DH, Ryu MH, Kang YK.
Conflicts of Interest
Conflicts of interest relevant to this article was not reported.
Clinical characteristic | Total (n=5,384) | 2000–2003 (n=880, 16.3%) | 2004–2007 (n=1,573, 29.2%) | 2008–2011 (n=1,435, 26.7%) | 2012–2015 (n=1,496, 27.8%) | p for trend |
---|---|---|---|---|---|---|
First-line chemotherapy | ||||||
Singlea) | 772 (14.3) | 94 (10.7) | 440 (28.0) | 148 (10.3) | 90 (6.0) | < 0.001 |
Doubletb) | 3,429 (63.7) | 622 (70.7) | 924 (58.7) | 946 (65.9) | 937 (62.6) | |
Doublet/Tmabc) | 288 (5.3) | - | 7 (0.4) | 53 (3.7) | 228 (15.2) | |
Doublet/Noveld) | 287 (5.3) | - | 53 (3.4) | 147 (10.2) | 87 (5.8) | |
Triplete) | 343 (6.4) | 79 (9.0) | 125 (7.9) | 86 (6.0) | 53 (3.5) | |
Others | 265 (4.9) | 85 (9.7) | 24 (1.5) | 55 (3.8) | 101 (6.8) | |
Second-line chemotherapy | ||||||
Received | 2,945 (54.7) | 409 (46.4) | 859 (54.5) | 833 (58.1) | 844 (56.5) | < 0.001 |
Singlea) | 1,267 (43.0) | 115 (28.1) | 408 (47.5) | 401 (48.1) | 343 (40.6) | < 0.001 |
Doubletb) | 1,333 (63.8) | 261 (50.6) | 435 (37.2) | 310 (38.7) | 327 (45.3) | |
Single/Rmabf) | 39 (1.3) | - | - | - | 39 (4.6) | |
Others | 306 (10.4) | 33 (8.1) | 16 (1.9) | 122 (14.6) | 135 (16.0) | |
Third-line chemotherapy | ||||||
Received | 1,527 (51.9) | 167 (40.8) | 432 (50.3) | 459 (55.1) | 469 (55.6) | < 0.001 |
Singlea) | 350 (22.9) | 48 (28.7) | 64 (14.8) | 88 (19.2) | 150 (32.0) | < 0.001 |
Doubletb) | 1,033 (67.6) | 107 (64.1) | 361 (83.6) | 327 (71.2) | 238 (50.7) | |
Immunotherapyg) | 19 (1.2) | - | - | - | 19 (4.1) | |
Others | 125 (8.2) | 12 (7.2) | 7 (1.6) | 44 (9.6) | 62 (13.2) |
Values are presented as number (%).
a) Single: fluoropyrimidine (F), taxane (T), or irinotecan (I),
b) Doublet: F/platinum (P), T/P, F/I, F/T, T/I, anthracycline (A)/P, A/F,
c) Doublet/Tmab: F/P with trastuzumab,
d) Doublet/Novel: F/P with novel agents in clinical trials,
e) Triplet: F/P/T,
f) Single/Rmab: T with ramucirumab,
g) Immunotherapy: immune checkpoint inhibitors.
Chemotherapy | Total (n=2,525) | Singlea) (n=357) | Doubletb) (n=1,426) | Doublet/Tmabc)(n=217) | Doublet/Noveld) (n=214) | Triplete) (n=189) |
---|---|---|---|---|---|---|
CR/PR | 1,113 (44.4) | 74 (20.7) | 627 (44.0) | 147 (67.7) | 115 (53.7) | 112 (59.3) |
SD | 655 (25.9) | 97 (27.2) | 382 (26.8) | 39 (18.0) | 64 (29.9) | 36 (19.0) |
PD | 391 (15.5) | 106 (29.7) | 217 (15.2) | 11 (5.1) | 14 (6.5) | 10 (5.3) |
NE | 366 (14.5) | 80 (22.4) | 200 (14.0) | 20 (9.2) | 21 (9.8) | 31 (16.4) |
Values are presented as number (%). CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease.
a) Single: fluoropyrimidine (F), taxane (T), or irinotecan (I),
b) Doublet: F/platinum (P), T/P, F/I, F/T, T/I, anthracycline (A)/P, A/F,
c) Doublet/Tmab: F/P with trastuzumab,
d) Doublet/Novel: F/P with novel agents in clinical trials,
e) Triplet: F/P/T.
Patient characteristics at first-line chemotherapy according to the treatment periods
Clinical characteristic | Total (n=5,384, 100%) | 2000–2003 (n=880, 16.3%) | 2004–2007 (n=1,573, 29.2%) | 2008–2011 (n=1,435, 26.7%) | 2012–2015 (n=1,496, 27.8%) | p for trend |
---|---|---|---|---|---|---|
Male sex | 3,521 (65.4) | 582 (66.1) | 1,023 (65.0) | 952 (66.3) | 964 (64.4) | 0.688 |
Age (yr) | ||||||
Median (range) | 56 (19–91) | 54 (19–78) | 57 (20–87) | 57 (20–91) | 57 (19–91) | < 0.001 |
≥ 65 | 1,415 (26.3) | 132 (15.0) | 426 (27.1) | 419 (29.2) | 438 (29.3) | < 0.001 |
ECOG PS | ||||||
0/1 | 4,773 (88.8) | 835 (94.9) | 1,387 (88.2) | 1,245 (87.1) | 1,306 (87.7) | < 0.001 |
2/3 | 600 (11.2) | 45 (5.1) | 186 (11.8) | 185 (12.9) | 184 (12.3) | |
Gastrectomy, done | 2,387 (44.3) | 409 (46.5) | 735 (46.7) | 620 (43.2%) | 623 (41.6) | 0.015 |
Histology | ||||||
WD/MD | 1,433 (26.6) | 206 (23.4) | 405 (25.7) | 395 (27.5) | 427 (28.5) | < 0.001 |
PD/SRC/Undiff | 3,363 (62.5) | 568 (64.5) | 890 (56.6) | 885 (61.7) | 1,020 (68.2) | |
Unclassified | 588 (10.9) | 106 (12.0) | 278 (17.7) | 155 (10.8) | 49 (3.3) | |
Status | ||||||
Recurrent | 1,941 (36.1) | 303 (34.4) | 599 (38.1) | 510 (35.5) | 529 (35.4) | 0.233 |
Initially advanced | 3,443 (63.9) | 577 (65.6) | 974 (61.9) | 925 (64.5) | 967 (64.6) | |
Metastatic sites, 2 or more | 1,935 (36.2) | 233 (26.5) | 509 (32.4) | 560 (39.5) | 633 (42.8) | < 0.001 |
Peritoneal, metastasis | 2,534 (47.2) | 377 (42.8) | 688 (43.7) | 750 (52.7) | 719 (48.4) | < 0.001 |
Liver, metastasis | 1,338 (25.0) | 224 (25.5) | 426 (27.1) | 355 (24.9) | 333 (22.5) | 0.033 |
Lung, metastasis | 269 (5.0) | 33 (3.8) | 82 (5.2) | 68 (4.8) | 86 (5.8) | 0.156 |
Bone, metastasis | 396 (7.4) | 49 (5.6) | 112 (7.1) | 106 (7.5) | 129 (8.7) | 0.041 |
ALP > 120 IU/L | 1,159 (21.8) | 261 (29.8) | 297 (19.1) | 286 (20.3) | 315 (21.1) | < 0.001 |
Albumin < 3.3 g/dL | 1,462 (27.4) | 216 (24.6) | 465 (29.9) | 368 (26.2) | 413 (27.7) | 0.025 |
Total bilirubin > 1.2 mg/dL | 368 (6.9) | 59 (6.8) | 114 (7.4) | 100 (7.1) | 95 (6.4) | 0.722 |
Prognostic score | ||||||
0–1 (good) | 2,313 (43.0) | 379 (43.1) | 695 (44.2) | 604 (42.2) | 635 (42.4) | < 0.001 |
2–3 (moderate) | 2,287 (42.5) | 430 (48.9) | 642 (40.8) | 597 (41.7) | 618 (41.3) | |
4 or more (poor) | 779 (14.5) | 71 (8.1) | 236 (15.0) | 229 (16.0) | 243 (16.2) |
Value are presented as number (%) unless otherwise indicated. ALP, alkaline phosphatase; ECOG PS, Eastern Cooperative Oncology Group Performance Status; MD, moderately differentiated; PD, poorly differentiated; SRC, signet ring cell; Undiff, undifferentiated; WD, well-differentiated.
Treatment characteristics according to the treatment periods
Clinical characteristic | Total (n=5,384) | 2000–2003 (n=880, 16.3%) | 2004–2007 (n=1,573, 29.2%) | 2008–2011 (n=1,435, 26.7%) | 2012–2015 (n=1,496, 27.8%) | p for trend |
---|---|---|---|---|---|---|
First-line chemotherapy | ||||||
Single |
772 (14.3) | 94 (10.7) | 440 (28.0) | 148 (10.3) | 90 (6.0) | < 0.001 |
Doublet |
3,429 (63.7) | 622 (70.7) | 924 (58.7) | 946 (65.9) | 937 (62.6) | |
Doublet/Tmab |
288 (5.3) | - | 7 (0.4) | 53 (3.7) | 228 (15.2) | |
Doublet/Novel |
287 (5.3) | - | 53 (3.4) | 147 (10.2) | 87 (5.8) | |
Triplet |
343 (6.4) | 79 (9.0) | 125 (7.9) | 86 (6.0) | 53 (3.5) | |
Others | 265 (4.9) | 85 (9.7) | 24 (1.5) | 55 (3.8) | 101 (6.8) | |
Second-line chemotherapy | ||||||
Received | 2,945 (54.7) | 409 (46.4) | 859 (54.5) | 833 (58.1) | 844 (56.5) | < 0.001 |
Single |
1,267 (43.0) | 115 (28.1) | 408 (47.5) | 401 (48.1) | 343 (40.6) | < 0.001 |
Doublet |
1,333 (63.8) | 261 (50.6) | 435 (37.2) | 310 (38.7) | 327 (45.3) | |
Single/Rmab |
39 (1.3) | - | - | - | 39 (4.6) | |
Others | 306 (10.4) | 33 (8.1) | 16 (1.9) | 122 (14.6) | 135 (16.0) | |
Third-line chemotherapy | ||||||
Received | 1,527 (51.9) | 167 (40.8) | 432 (50.3) | 459 (55.1) | 469 (55.6) | < 0.001 |
Single |
350 (22.9) | 48 (28.7) | 64 (14.8) | 88 (19.2) | 150 (32.0) | < 0.001 |
Doublet |
1,033 (67.6) | 107 (64.1) | 361 (83.6) | 327 (71.2) | 238 (50.7) | |
Immunotherapy |
19 (1.2) | - | - | - | 19 (4.1) | |
Others | 125 (8.2) | 12 (7.2) | 7 (1.6) | 44 (9.6) | 62 (13.2) |
Values are presented as number (%).
a)Single: fluoropyrimidine (F), taxane (T), or irinotecan (I),
b)Doublet: F/platinum (P), T/P, F/I, F/T, T/I, anthracycline (A)/P, A/F,
c)Doublet/Tmab: F/P with trastuzumab,
d)Doublet/Novel: F/P with novel agents in clinical trials,
e)Triplet: F/P/T,
f)Single/Rmab: T with ramucirumab,
g)Immunotherapy: immune checkpoint inhibitors.
Response rate in patients with measurable disease according to the first-line treatment
Chemotherapy | Total (n=2,525) | Single |
Doublet |
Doublet/Tmab |
Doublet/Novel |
Triplet |
---|---|---|---|---|---|---|
CR/PR | 1,113 (44.4) | 74 (20.7) | 627 (44.0) | 147 (67.7) | 115 (53.7) | 112 (59.3) |
SD | 655 (25.9) | 97 (27.2) | 382 (26.8) | 39 (18.0) | 64 (29.9) | 36 (19.0) |
PD | 391 (15.5) | 106 (29.7) | 217 (15.2) | 11 (5.1) | 14 (6.5) | 10 (5.3) |
NE | 366 (14.5) | 80 (22.4) | 200 (14.0) | 20 (9.2) | 21 (9.8) | 31 (16.4) |
Values are presented as number (%). CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease.
a)Single: fluoropyrimidine (F), taxane (T), or irinotecan (I),
b)Doublet: F/platinum (P), T/P, F/I, F/T, T/I, anthracycline (A)/P, A/F,
c)Doublet/Tmab: F/P with trastuzumab,
d)Doublet/Novel: F/P with novel agents in clinical trials,
e)Triplet: F/P/T.
Value are presented as number (%) unless otherwise indicated. ALP, alkaline phosphatase; ECOG PS, Eastern Cooperative Oncology Group Performance Status; MD, moderately differentiated; PD, poorly differentiated; SRC, signet ring cell; Undiff, undifferentiated; WD, well-differentiated.
Values are presented as number (%). Single: fluoropyrimidine (F), taxane (T), or irinotecan (I), Doublet: F/platinum (P), T/P, F/I, F/T, T/I, anthracycline (A)/P, A/F, Doublet/Tmab: F/P with trastuzumab, Doublet/Novel: F/P with novel agents in clinical trials, Triplet: F/P/T, Single/Rmab: T with ramucirumab, Immunotherapy: immune checkpoint inhibitors.
Values are presented as number (%). CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease. Single: fluoropyrimidine (F), taxane (T), or irinotecan (I), Doublet: F/platinum (P), T/P, F/I, F/T, T/I, anthracycline (A)/P, A/F, Doublet/Tmab: F/P with trastuzumab, Doublet/Novel: F/P with novel agents in clinical trials, Triplet: F/P/T.