Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study

Background The first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti‐epidermal growth factor receptor (anti‐EGFR) monoclonal antibody (mAb) is the more effective addition to a chemoth...

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Published inCancer medicine (Malden, MA) Vol. 12; no. 14; pp. 15176 - 15186
Main Authors Liang, Yi‐Hsin, Chen, Kuo‐Hsing, Shao, Yu‐Yun
Format Journal Article
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.07.2023
John Wiley and Sons Inc
Wiley
Subjects
Bevacizumab
Cancer therapies
cetuximab
Chemotherapy
Clinical outcomes
Clinical trials
Colorectal cancer
Colorectal carcinoma
Demographics
Drug dosages
EGFR
Epidermal growth factor
Epidermal growth factor receptors
Histology
K-Ras protein
Lung cancer
Metastases
Metastasis
metastatic colorectal cancer
Monoclonal antibodies
Multivariate analysis
National health insurance
panitumumab
Patients
Population
secondary surgery
Surgery
Tumors
Variables
Taiwan
bevacizumab
cetuximab
metastatic colorectal cancer
panitumumab
secondary surgery
EGFR
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Abstract Background The first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti‐epidermal growth factor receptor (anti‐EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first‐line treatment for inoperable KRAS wild‐type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti‐EGFR mAb needs to be addressed. Methods We established a cohort of patients with KRAS wild‐type mCRC who were treated with first‐line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation. Results A total of 6482 patients were included; bevacizumab and anti‐EGFR mAb were the first‐line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti‐EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left‐sided primary tumors, the OS and TTF benefits of anti‐EGFR mAb remained. Among right‐sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first‐line anti‐EGFR mAb therapy remained an independent predictor of longer OS and TTF for left‐sided primary tumors. Patients who received anti‐EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab. Conclusion For patients who received first‐line doublet chemotherapy for KRAS wild‐type mCRC, adding anti‐EGFR mAb was associated with significantly longer OS and TTF, especially for left‐sided primary tumors. Anti‐EGFR mAb was associated with significantly longer OS and TTF than the addition of bevacizumab.
AbstractList Abstract Background The first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti‐epidermal growth factor receptor (anti‐EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first‐line treatment for inoperable KRAS wild‐type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti‐EGFR mAb needs to be addressed. Methods We established a cohort of patients with KRAS wild‐type mCRC who were treated with first‐line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation. Results A total of 6482 patients were included; bevacizumab and anti‐EGFR mAb were the first‐line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti‐EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left‐sided primary tumors, the OS and TTF benefits of anti‐EGFR mAb remained. Among right‐sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first‐line anti‐EGFR mAb therapy remained an independent predictor of longer OS and TTF for left‐sided primary tumors. Patients who received anti‐EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab. Conclusion For patients who received first‐line doublet chemotherapy for KRAS wild‐type mCRC, adding anti‐EGFR mAb was associated with significantly longer OS and TTF, especially for left‐sided primary tumors.
BackgroundThe first-line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first-line treatment for inoperable KRAS wild-type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti-EGFR mAb needs to be addressed.MethodsWe established a cohort of patients with KRAS wild-type mCRC who were treated with first-line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation.ResultsA total of 6482 patients were included; bevacizumab and anti-EGFR mAb were the first-line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti-EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left-sided primary tumors, the OS and TTF benefits of anti-EGFR mAb remained. Among right-sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first-line anti-EGFR mAb therapy remained an independent predictor of longer OS and TTF for left-sided primary tumors. Patients who received anti-EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab.ConclusionFor patients who received first-line doublet chemotherapy for KRAS wild-type mCRC, adding anti-EGFR mAb was associated with significantly longer OS and TTF, especially for left-sided primary tumors.
The first-line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first-line treatment for inoperable KRAS wild-type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti-EGFR mAb needs to be addressed.BACKGROUNDThe first-line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first-line treatment for inoperable KRAS wild-type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti-EGFR mAb needs to be addressed.We established a cohort of patients with KRAS wild-type mCRC who were treated with first-line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation.METHODSWe established a cohort of patients with KRAS wild-type mCRC who were treated with first-line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation.A total of 6482 patients were included; bevacizumab and anti-EGFR mAb were the first-line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti-EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left-sided primary tumors, the OS and TTF benefits of anti-EGFR mAb remained. Among right-sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first-line anti-EGFR mAb therapy remained an independent predictor of longer OS and TTF for left-sided primary tumors. Patients who received anti-EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab.RESULTSA total of 6482 patients were included; bevacizumab and anti-EGFR mAb were the first-line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti-EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left-sided primary tumors, the OS and TTF benefits of anti-EGFR mAb remained. Among right-sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first-line anti-EGFR mAb therapy remained an independent predictor of longer OS and TTF for left-sided primary tumors. Patients who received anti-EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab.For patients who received first-line doublet chemotherapy for KRAS wild-type mCRC, adding anti-EGFR mAb was associated with significantly longer OS and TTF, especially for left-sided primary tumors.CONCLUSIONFor patients who received first-line doublet chemotherapy for KRAS wild-type mCRC, adding anti-EGFR mAb was associated with significantly longer OS and TTF, especially for left-sided primary tumors.
The first-line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first-line treatment for inoperable KRAS wild-type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti-EGFR mAb needs to be addressed. We established a cohort of patients with KRAS wild-type mCRC who were treated with first-line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation. A total of 6482 patients were included; bevacizumab and anti-EGFR mAb were the first-line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti-EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left-sided primary tumors, the OS and TTF benefits of anti-EGFR mAb remained. Among right-sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first-line anti-EGFR mAb therapy remained an independent predictor of longer OS and TTF for left-sided primary tumors. Patients who received anti-EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab. For patients who received first-line doublet chemotherapy for KRAS wild-type mCRC, adding anti-EGFR mAb was associated with significantly longer OS and TTF, especially for left-sided primary tumors.
Anti‐EGFR mAb was associated with significantly longer OS and TTF than the addition of bevacizumab.
Background The first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti‐epidermal growth factor receptor (anti‐EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first‐line treatment for inoperable KRAS wild‐type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti‐EGFR mAb needs to be addressed. Methods We established a cohort of patients with KRAS wild‐type mCRC who were treated with first‐line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation. Results A total of 6482 patients were included; bevacizumab and anti‐EGFR mAb were the first‐line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti‐EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left‐sided primary tumors, the OS and TTF benefits of anti‐EGFR mAb remained. Among right‐sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first‐line anti‐EGFR mAb therapy remained an independent predictor of longer OS and TTF for left‐sided primary tumors. Patients who received anti‐EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab. Conclusion For patients who received first‐line doublet chemotherapy for KRAS wild‐type mCRC, adding anti‐EGFR mAb was associated with significantly longer OS and TTF, especially for left‐sided primary tumors. Anti‐EGFR mAb was associated with significantly longer OS and TTF than the addition of bevacizumab.
Author Liang, Yi‐Hsin
Shao, Yu‐Yun
Chen, Kuo‐Hsing
AuthorAffiliation 3 Department of Oncology National Taiwan University Hospital Taipei Taiwan
1 Graduate Institutes of Oncology National Taiwan University College of Medicine Taipei Taiwan
4 Department of Medical Oncology National Taiwan University Cancer Center Taipei Taiwan
2 Center of Genomic and Precision Medicine National Taiwan University College of Medicine Taipei Taiwan
AuthorAffiliation_xml – name: 1 Graduate Institutes of Oncology National Taiwan University College of Medicine Taipei Taiwan
– name: 4 Department of Medical Oncology National Taiwan University Cancer Center Taipei Taiwan
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– name: 2 Center of Genomic and Precision Medicine National Taiwan University College of Medicine Taipei Taiwan
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  surname: Shao
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/37325970$$D View this record in MEDLINE/PubMed
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Issue 14
Keywords bevacizumab
cetuximab
metastatic colorectal cancer
panitumumab
secondary surgery
EGFR
Language English
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2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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Snippet Background The first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet....
The first-line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether...
BackgroundThe first-line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet....
Anti‐EGFR mAb was associated with significantly longer OS and TTF than the addition of bevacizumab.
Abstract Background The first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy...
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StartPage 15176
SubjectTerms Bevacizumab
Cancer therapies
cetuximab
Chemotherapy
Clinical outcomes
Clinical trials
Colorectal cancer
Colorectal carcinoma
Demographics
Drug dosages
EGFR
Epidermal growth factor
Epidermal growth factor receptors
Histology
K-Ras protein
Lung cancer
Metastases
Metastasis
metastatic colorectal cancer
Monoclonal antibodies
Multivariate analysis
National health insurance
panitumumab
Patients
Population
secondary surgery
Surgery
Tumors
Variables
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Title Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study
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