1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
3Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
4Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
5Division of Medical Oncology, National Cancer Centre Singapore, Singapore
6Department of Medicine, San Juan De Dios Hospital, Manila, Philippines
7Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
8Department of Medical Oncology and Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea
9Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
10Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China
11The Center for Anti-Cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, Korea
12Department of Hematology-Oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
13Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea
14Division of Hematology-Oncology, Inha University Hospital, Incheon, Korea
15Department of Hematology-Oncology, Pusan National University Hospital, Busan, Korea
16Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea
17Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
18Novartis Pharmaceuticals Corporation, APSA, Midrand, South Africa
19Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
Copyright © 2019 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.
Sung-Bae Kim has received funding from Novartis, Sanofi Aventis, Kyowa Kirim Inc., Dongkook Pharmaceuticals Company Ltd. Gerardo Cornelio has received funding from Renovo; has served as a consultant/advisory role for Astra Zeneca Oncology, BF, MSD Oncology, and Esai Oncology. Yoon Sim Yap has served as a consultant/advisory role from Novartis. Soonmyung Paik has received funding from GSK for this study; has served as a consultant/advisory role for Leica Biosystems. Christos Nathaniel is an employee of Novartis Pharmaceuticals Corporation. The following authors have nothing to disclose: In-Gu Do, Janice Tsang, Tae-You Kim, Gyungyub Gong, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, and Jungsil Ro.
Characteristic | No. (%) (n=154) |
---|---|
Age distribution at primary diagnosis (yr) | |
Mean±SD | 48.1±9.8 |
Median (range) | 52.9 (24.8-76.5) |
< 50 yr vs. ≥ 50 yr | 85 (55.2):69 (44.8) |
Age distribution at study entry (yr) | |
Mean±SD | 52.4±9.9 |
Median (range) | 48.7 (28.3-86.0) |
< 50 yr vs. ≥ 50 yr | 62 (40.3):92 (59.7) |
Time between primary diagnosis and study entry (yr) | |
Mean±SD | 4.3±3.2 |
Median (range) | 3.3 (0.2-19.9) |
Postmenopausal | |
At primary diagnosis | 78 (50.6) |
At study entry | 131 (85.1) |
ECOG PS | |
0 | 42 (27.3) |
1 | 107 (69.5) |
2 | 5 (3.2) |
Ethnicity | |
Korean | 110 (71.4) |
Chinese | 40 (26.0) |
Filipino | 2 (1.3) |
Malay | 2 (1.3) |
Cancer stage(s)a) | |
At primary diagnosis | |
I, II, or III | 118 (76.7) |
IV (de novo) | 34 (22.1) |
Unknown | 2 (1.3) |
At study entryb) | |
I, II, or III (metastatic) | 2 (1.3) |
IV (de novo) | 150 (97.4) |
Unknown | 0 |
HER2 status | |
At primary diagnosis | |
Positive | 147 (95.5) |
Negative | 2 (1.3) |
Not performed | 5 (3.2) |
At study entry | |
Positive | 45 (29.2) |
Negative | 0 |
Not done | 109 (70.8) |
ER status | |
At primary diagnosis | |
Positive | 65 (42.2) |
Negative | 85 (55.2) |
Unknown | 4 (2.6) |
At study entry | |
Positive | 20 (13.0) |
Negative | 22 (14.3) |
Unknown | 112 (72.7) |
Regimen numbera) | Trastuzumab | Lapatinib | Taxane |
---|---|---|---|
Prior to study entryb) | |||
1 (adjuvant; n=129) | 87 (67.4) | 2 (1.6) | 85 (65.9) |
2 (metastatic first-line; n=82) | 22 (26.8) | 9 (11.0) | 16 (19.5) |
≥ 3 (metastatic second-line or greater; n=100) | 14 (14.0) | 25 (25.0) | 11 (11.0) |
After study entryc) | |||
1 (n=24) | 0 | 24 (100) | 1 (4.2) |
2 (n=50) | 0 | 48 (96.0) | 0 |
≥ 3 (n=103) | 17 (16.5) | 65 (63.1) | 5 (4.9) |
Values are presented as number (%).
a) Systemic therapy for recurrent/metastatic disease,
b) Data was only available for 153 patients prior to study entry because 1 in the analysis population did not have data,
c) Data were only available for 138 patients after study entry because 16 in the analysis population did not have data.
Other therapies not reported include anthracyclines, hormonal therapy, and other chemotherapy and targeted therapy.
Response | No. (%) |
---|---|
CR | 6 (3.9) |
PR | 20 (13.0) |
Stable disease | 26 (16.9) |
Progressive disease | 86 (55.8) |
Unable to determine | 16 (10.4) |
Total | 154 (100) |
RR | 26 (16.9)a) |
Unadjusted HR (95% CI)a) | p-valueb) | Adjusted HR (95% CI) | p-valuec) | |
---|---|---|---|---|
p95HER2 expression | 0.85 (0.44-1.60) | 0.628 | 1.01 (0.45-2.20) | 0.975 |
PTEN deletion/down-regulation | 0.84 (0.53-1.30) | 0.456 | 1.30 (0.60-3.00) | 0.488 |
PIK3CA mutation | 1.20 (0.75-1.90) | 0.476 | 1.20 (0.50-2.70) | 0.649 |
Ethnic group: Malayd) | 2.90 (0.70-12.70) | 0.149 | 3.70 (0.70-19.80) | 0.121 |
Ethnic group: Koreand) | 2.10 (1.30-3.50) | 0.004 | 2.00 (0.99-4.10) | 0.051 |
Contralateral breast | 0.37 (0.14-0.99) | 0.047 | 0.30 (0.08-1.10) | 0.078 |
PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; p95HER2, truncated human epidermal growth factor receptor 2; PTEN, phosphatase and tensin homolog; PIK3CA, phosphatidylinositol 3 kinase (catalytic subunit).
a) Univariate analysis,
b) Log-rank test of survival distribution equality for subgroups defined by positive and negative biomarker status,
c) From Cox proportional hazards model adjusted for prognostic factors that are found to be significantly related to PFS on lapatinib in the univariable analysis for primary endpoint and 3 biomarkers (p95HER2 protein expression, PTEN deletion/downregulation, and PIK3CA mutation),
d) Reference group: Chinese.
Characteristic | No. (%) (n=154) |
---|---|
Age distribution at primary diagnosis (yr) | |
Mean±SD | 48.1±9.8 |
Median (range) | 52.9 (24.8-76.5) |
< 50 yr vs. ≥ 50 yr | 85 (55.2):69 (44.8) |
Age distribution at study entry (yr) | |
Mean±SD | 52.4±9.9 |
Median (range) | 48.7 (28.3-86.0) |
< 50 yr vs. ≥ 50 yr | 62 (40.3):92 (59.7) |
Time between primary diagnosis and study entry (yr) | |
Mean±SD | 4.3±3.2 |
Median (range) | 3.3 (0.2-19.9) |
Postmenopausal | |
At primary diagnosis | 78 (50.6) |
At study entry | 131 (85.1) |
ECOG PS | |
0 | 42 (27.3) |
1 | 107 (69.5) |
2 | 5 (3.2) |
Ethnicity | |
Korean | 110 (71.4) |
Chinese | 40 (26.0) |
Filipino | 2 (1.3) |
Malay | 2 (1.3) |
Cancer stage(s) |
|
At primary diagnosis | |
I, II, or III | 118 (76.7) |
IV (de novo) | 34 (22.1) |
Unknown | 2 (1.3) |
At study entry |
|
I, II, or III (metastatic) | 2 (1.3) |
IV (de novo) | 150 (97.4) |
Unknown | 0 |
HER2 status | |
At primary diagnosis | |
Positive | 147 (95.5) |
Negative | 2 (1.3) |
Not performed | 5 (3.2) |
At study entry | |
Positive | 45 (29.2) |
Negative | 0 |
Not done | 109 (70.8) |
ER status | |
At primary diagnosis | |
Positive | 65 (42.2) |
Negative | 85 (55.2) |
Unknown | 4 (2.6) |
At study entry | |
Positive | 20 (13.0) |
Negative | 22 (14.3) |
Unknown | 112 (72.7) |
Regimen number |
Trastuzumab | Lapatinib | Taxane |
---|---|---|---|
Prior to study entry |
|||
1 (adjuvant; n=129) | 87 (67.4) | 2 (1.6) | 85 (65.9) |
2 (metastatic first-line; n=82) | 22 (26.8) | 9 (11.0) | 16 (19.5) |
≥ 3 (metastatic second-line or greater; n=100) | 14 (14.0) | 25 (25.0) | 11 (11.0) |
After study entry |
|||
1 (n=24) | 0 | 24 (100) | 1 (4.2) |
2 (n=50) | 0 | 48 (96.0) | 0 |
≥ 3 (n=103) | 17 (16.5) | 65 (63.1) | 5 (4.9) |
Response | No. (%) |
---|---|
CR | 6 (3.9) |
PR | 20 (13.0) |
Stable disease | 26 (16.9) |
Progressive disease | 86 (55.8) |
Unable to determine | 16 (10.4) |
Total | 154 (100) |
RR | 26 (16.9) |
Unadjusted HR (95% CI) |
p-value |
Adjusted HR (95% CI) | p-value |
|
---|---|---|---|---|
p95HER2 expression | 0.85 (0.44-1.60) | 0.628 | 1.01 (0.45-2.20) | 0.975 |
PTEN deletion/down-regulation | 0.84 (0.53-1.30) | 0.456 | 1.30 (0.60-3.00) | 0.488 |
PIK3CA mutation | 1.20 (0.75-1.90) | 0.476 | 1.20 (0.50-2.70) | 0.649 |
Ethnic group: Malay |
2.90 (0.70-12.70) | 0.149 | 3.70 (0.70-19.80) | 0.121 |
Ethnic group: Korean |
2.10 (1.30-3.50) | 0.004 | 2.00 (0.99-4.10) | 0.051 |
Contralateral breast | 0.37 (0.14-0.99) | 0.047 | 0.30 (0.08-1.10) | 0.078 |
SD, standard deviation; ECOG PS, Eastern Cooperative Oncology Group performance status; HER2, human epidermal growth factor receptor 2; ER, estrogen receptor. According to the American Joint Committee on Cancer 7th edition, Data were not recorded for all patients.
Values are presented as number (%). Systemic therapy for recurrent/metastatic disease, Data was only available for 153 patients prior to study entry because 1 in the analysis population did not have data, Data were only available for 138 patients after study entry because 16 in the analysis population did not have data. Other therapies not reported include anthracyclines, hormonal therapy, and other chemotherapy and targeted therapy.
RR, response rate; CR, complete response; PR, partial response. Patients with CR or PR.
PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; p95HER2, truncated human epidermal growth factor receptor 2; PTEN, phosphatase and tensin homolog; Univariate analysis, Log-rank test of survival distribution equality for subgroups defined by positive and negative biomarker status, From Cox proportional hazards model adjusted for prognostic factors that are found to be significantly related to PFS on lapatinib in the univariable analysis for primary endpoint and 3 biomarkers (p95HER2 protein expression, PTEN deletion/downregulation, and Reference group: Chinese.