1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
3Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea
4Cancer Research Institute, Seoul National University, Seoul, Korea
5Center for Breast Cancer, National Cancer Center, Goyang, Korea
6Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
7Division of Medical Oncology and Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
8Division of Hematology-Oncology, Samsung Medical Center, Seoul, Korea
9Department of Internal Medicine, Inha University Hospital, Incheon, Korea
10Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
11Department of Hematology and Oncology, Ewha Womans University Medical Center, Seoul, Korea
12Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
13Department of Medical Oncology and Hematology, Kyung Hee University Hospital, Seoul, Korea
Copyright © 2023 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.
Ethical Statement
The study protocol was reviewed and approved by the institutional review board of each participating center. Written informed consent was obtained from each patient before enrollment. This study was carried out in accordance with the recommendations of the Declaration of Helsinki for biomedical research involving human subjects and the Guidelines for Good Clinical Practice (ClinicalTrial.gov Identifier: NCT00527930).
Author Contributions
Conceived and designed the analysis: Lee DW, Keam B, Im SA.
Collected the data: Lee DW, Keam B, Lee KS, Ahn JH, Sohn J, Ahn JS, Lee MH, Kim JH, Lee KE, Kim HJ, Kim SY, Park YH, Ock CY, Lee KH, Han SW, Kim SB, Im YH, Chung HC, Oh DY, Im SA.
Contributed data or analysis tools: Lee DW, Keam B, Lee KS, Ahn JH, Sohn J, Ahn JS, Lee MH, Kim JH, Lee KE, Kim HJ, Kim SY, Park YH, Ock CY, Lee KH, Han SW, Kim SB, Im YH, Chung HC, Oh DY, Im SA.
Performed the analysis: Lee DW, Keam B, Lee KS, Ahn JH, Sohn J, Ahn JS, Lee MH, Kim JH, Lee KE, Kim HJ, Kim SY, Park YH, Ock CY, Lee KH, Han SW, Kim SB, Im YH, Chung HC, Oh DY.
Wrote the paper: Lee DW, Keam B, Ock CY, Im SA.
Manuscript review and final approval: Lee DW, Keam B, Lee KS, Ahn JH, Sohn J, Ahn JS, Lee MH, Kim JH, Lee KE, Kim HJ, Kim SY, Park YH, Ock CY, Lee KH, Han SW, Kim SB, Im YH, Chung HC, Oh DY, Im SA.
Conflicts of Interest
SA Im received research fund from AstraZeneca, Daewoong Pharm, Eisai, Pfizer, and Roche outside of the current work and have been work as advisory board for AstraZeneca, Amgen, Eisai, GSK, Hanmi Corp., Lilly, MSD, Novartis, Pfizer, and Roche.
DY Oh received research fund from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, and Handok outside of the current work and have been work as advisory board for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, and Yuhan.
SB Kim received research fund from Novartis, Sanofi-Aventis, and DongKook Pharm Co. outside of the current work, have been work as advisory board for Novartis, AstraZeneca, Lilly, Dae Hwa Pharmaceutical Co. Ltd, ISU Abxis, and Daiichi-Sankyo, and has stock in Genopeaks, and NeogeneTC.
JH Kim received research fund from Ono Korea Ltd outside of the current work and attended advisory board for BIXINK, Daichii Sankyo, Eisai, Lilly, Novartis, Pfizer, and Roche.
KS Lee reports grants from Dong-A Socio outside of the current work and have been work as advisory board for Eli Lilly, Novartis, Pfizer, Roche, and Bixink.
TS-1 was supported by Taiho Pharmaceutical and Jeil Pharmaceutical. Oxaliplatin was supported by Sanofi-Aventis.
Baseline characteristics
No. of patients (%) (n=87) | |
---|---|
Age (yr) | |
Median (range) | 48 (30–71) |
< 50 | 49 (56.3) |
≥ 50 | 38 (43.7) |
ECOG PS | |
0 | 35 (40.2) |
1 | 48 (55.2) |
2 | 4 (4.6) |
Menopausal status | |
Premenopausal | 29 (33.3) |
Postmenopausal | 56 (64.4) |
Unknown | 2 (2.3) |
Disease status | |
Initial metastatic breast cancer | 19 (21.8) |
Recurred/Relapsed breast cancer | 68 (78.2) |
Hormone receptor status | |
ER− or PR-positive | 54 (62.1) |
ER− and PR-negative | 33 (37.9) |
HER2 status | |
Positive | 6 (6.9) |
Negative | 81 (93.1) |
Metastases sites | |
Visceral metastasis | 74 (85.1) |
Bone metastasis | 55 (63.2) |
Chest wall/Soft tissue/Lymph node metastasis | 44 (50.6) |
No. of metastases sites | |
< 3 | 39 (44.8) |
≥ 3 | 48 (55.2) |
Prior chemotherapy | 87 (100) |
Neo− or adjuvant chemotherapy | 70 (80.5) |
Palliative chemotherapy | 80 (92.0) |
Prior-anthracycline | 87 (100) |
Prior-taxanes | 86 (98.9) |
Palliative chemotherapy line | |
3 | 1 (1.1) |
2 | 34 (39.1) |
1 | 45 (51.7) |
0 | 7 (8.0) |
ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor.
Univariate analysis of time to progression
No. (%) | TTP | p-value | |
---|---|---|---|
Age (yr) | |||
< 50 | 49 (56.3) | 5.8 (4.4–7.2) | 0.230 |
≥ 50 | 38 (43.7) | 6.7 (4.6–8.8) | |
ECOG PS | |||
0 | 35 (40.2) | 6.0 (3.4–8.6) | 0.021 |
1–2 | 52 (59.8) | 5.8 (4.7–6.9) | |
Hormone receptor status | |||
ER− or PR-positive | 54 (62.1) | 6.4 (5.7–7.1) | 0.078 |
ER− and PR-negative | 33 (37.9) | 3.8 (2.0–5.5) | |
Visceral metastasis | |||
Present | 74 (85.1) | 5.8 (4.7–6.9) | 0.075 |
None | 13 (14.9) | Not reached | |
No. of metastases sites | |||
< 3 | 39 (44.8) | 6.5 (5.6–7.4) | 0.088 |
≥ 3 | 48 (55.2) | 4.6 (2.6–6.7) | |
Palliative chemotherapy line | |||
2–3 | 35 (40.2) | 5.8 (4.5–7.1) | 0.340 |
0–1 | 52 (59.8) | 6.0 (4.4–7.5) |
ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; PR, progesterone receptor; TTP, time-to-progression.
Toxicity profile
Total | Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
---|---|---|---|---|---|
Hematology toxicity | |||||
Anemia | 73 (83.9) | 51 (58.6) | 20 (23.0) | 2 (2.3) | 0 |
Thrombocytopenia | 71 (81.6) | 18 (20.7) | 30 (34.5) | 18 (20.7) | 5 (5.7) |
Leucopenia | 68 (88.2) | 33 (37.9) | 31 (35.6) | 3 (3.4) | 1 (1.1) |
Neutropenia | 67 (77.0) | 11 (12.6) | 28 (32.2) | 23 (26.4) | 5 (5.7) |
Neutropenic fever | 0 | 0 | 0 | 0 | 0 |
Non-hematologic toxicity | |||||
Sensory neuropathy | 68 (78.2) | 49 (56.3) | 16 (18.4) | 3 (3.4) | 0 |
Nausea | 64 (73.6) | 36 (41.4) | 26 (29.9) | 2 (2.3) | 0 |
AST elevation | 64 (73.6) | 53 (60.9) | 9 (10.3) | 1 (1.1) | 1 (1.1) |
Anorexia | 47 (54.0) | 25 (28.7) | 20 (23.0) | 2 (2.3) | 0 |
Vomiting | 47 (54.0) | 26 (29.9) | 13 (14.9) | 8 (8.9) | 0 |
ALP elevation | 44 (50.6) | 34 (39.1) | 9 (10.3) | 1 (1.1) | 0 |
Diarrhea | 35 (40.2) | 17 (19.5) | 9 (10.3) | 9 (10.3) | 0 |
ALT elevation | 34 (39.1) | 31 (35.6) | 2 (2.3) | 0 | 1 (1.1) |
Stomatitis | 17 (19.5) | 14 (16.1) | 2 (2.3) | 1 (1.1) | 0 |
Constipation | 13 (14.9) | 9 (10.3) | 4 (4.6) | 0 | 0 |
Values are presented as number (%). ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase.
ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor.
ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; PR, progesterone receptor; TTP, time-to-progression.
Values are presented as number (%). ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase.