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Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer

IMPORTANCE: Professional society guidelines recommend treating patients with metastatic colorectal cancer with targeted therapies, including epithelial growth factor receptor (EGFR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors, depending on the presence or absence of certain m...

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Autores principales: Koroukian, Siran M., Booker, Benjamin D., Vu, Long, Schumacher, Fredrick R., Rose, Johnie, Cooper, Gregory S., Selfridge, J. Eva, Markt, Sarah C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857024/
https://www.ncbi.nlm.nih.gov/pubmed/36656585
http://dx.doi.org/10.1001/jamanetworkopen.2022.50030
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author Koroukian, Siran M.
Booker, Benjamin D.
Vu, Long
Schumacher, Fredrick R.
Rose, Johnie
Cooper, Gregory S.
Selfridge, J. Eva
Markt, Sarah C.
author_facet Koroukian, Siran M.
Booker, Benjamin D.
Vu, Long
Schumacher, Fredrick R.
Rose, Johnie
Cooper, Gregory S.
Selfridge, J. Eva
Markt, Sarah C.
author_sort Koroukian, Siran M.
collection PubMed
description IMPORTANCE: Professional society guidelines recommend treating patients with metastatic colorectal cancer with targeted therapies, including epithelial growth factor receptor (EGFR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors, depending on the presence or absence of certain mutations. Since most studies of first-line targeted therapies have been limited by sample size, there is a need for larger studies using data from routine clinical care. OBJECTIVES: To identify factors associated with receipt of first-line targeted therapies among patients with metastatic colorectal cancer for whom RAS or BRAF mutation data in the tumor were available and investigate whether targeted therapy is associated with survival. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used deidentified data from an electronic health record–derived database to include patients from 800 sites of patient care across the US who were diagnosed with de novo metastatic colorectal cancer between January 1, 2013, and March 31, 2020 (n = 9134). MAIN OUTCOMES AND MEASURES: Receipt of first-line targeted therapy, categorized as ever having received EGFR inhibitors, VEGF inhibitors, or neither. The secondary outcome was overall survival. RESULTS: The study population included 9134 patients. The median age at diagnosis was 62 years (IQR, 53-71 years), 5019 (54.9%) were male, and 5692 (62.3%) were White. The median follow-up period was 15 months. Overall, 713 patients (7.8%) received EGFR inhibitors and 5081 patients (55.6%) received VEGF inhibitors as part of their first-line treatment. Among patients with RAS wild-type (RAS-WT) tumors, 625 patients (15.5%) received EGFR inhibitors and 2053 patients (50.9%) received VEGF inhibitors. In patients with RAS mutant (RAS-Mut) tumors, 50 patients (1.1%) received EGFR inhibitors and 2682 patients (59.7%) received VEGF inhibitors; among those with BRAF-mutant (BRAF-Mut) tumors, 38 patients (6.3%) received EGFR inhibitors and 346 patients (57.2%) received VEGF inhibitors. More than one-third of the patients (36.6%) received neither EGFR inhibitors nor VEGF inhibitors. Compared with patients younger than age 40 years, those aged 80 years or older had significantly lower odds to receive targeted therapies (EGFR or VEGF inhibitors in patients with RAS-WT tumors: adjusted odds ratio [aOR], 0.53; 95% CI, 0.36-0.79; and VEGF inhibitors in patients with RAS-Mut tumors: aOR, 0.62; 95% CI, 0.42-0.90). Improved survival was associated with EGFR inhibitor therapy in patients with RAS-WT tumors (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.74-0.98). Unlike in clinical trials, however, no survival benefit was noted with use of VEGF inhibitors among patients with RAS-WT (aHR, 1.00; 95% CI, 0.91-1.11) or RAS-Mut (aHR, 1.01; 95% CI, 0.93-1.10) tumors. CONCLUSIONS AND RELEVANCE: The findings of this study showed mixed results on survival benefits associated with targeted therapy. In addition, given that some of the results differed from those of randomized clinical trials, this study highlights the importance of using data originating from routine clinical care.
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spelling pubmed-98570242023-02-03 Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer Koroukian, Siran M. Booker, Benjamin D. Vu, Long Schumacher, Fredrick R. Rose, Johnie Cooper, Gregory S. Selfridge, J. Eva Markt, Sarah C. JAMA Netw Open Original Investigation IMPORTANCE: Professional society guidelines recommend treating patients with metastatic colorectal cancer with targeted therapies, including epithelial growth factor receptor (EGFR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors, depending on the presence or absence of certain mutations. Since most studies of first-line targeted therapies have been limited by sample size, there is a need for larger studies using data from routine clinical care. OBJECTIVES: To identify factors associated with receipt of first-line targeted therapies among patients with metastatic colorectal cancer for whom RAS or BRAF mutation data in the tumor were available and investigate whether targeted therapy is associated with survival. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used deidentified data from an electronic health record–derived database to include patients from 800 sites of patient care across the US who were diagnosed with de novo metastatic colorectal cancer between January 1, 2013, and March 31, 2020 (n = 9134). MAIN OUTCOMES AND MEASURES: Receipt of first-line targeted therapy, categorized as ever having received EGFR inhibitors, VEGF inhibitors, or neither. The secondary outcome was overall survival. RESULTS: The study population included 9134 patients. The median age at diagnosis was 62 years (IQR, 53-71 years), 5019 (54.9%) were male, and 5692 (62.3%) were White. The median follow-up period was 15 months. Overall, 713 patients (7.8%) received EGFR inhibitors and 5081 patients (55.6%) received VEGF inhibitors as part of their first-line treatment. Among patients with RAS wild-type (RAS-WT) tumors, 625 patients (15.5%) received EGFR inhibitors and 2053 patients (50.9%) received VEGF inhibitors. In patients with RAS mutant (RAS-Mut) tumors, 50 patients (1.1%) received EGFR inhibitors and 2682 patients (59.7%) received VEGF inhibitors; among those with BRAF-mutant (BRAF-Mut) tumors, 38 patients (6.3%) received EGFR inhibitors and 346 patients (57.2%) received VEGF inhibitors. More than one-third of the patients (36.6%) received neither EGFR inhibitors nor VEGF inhibitors. Compared with patients younger than age 40 years, those aged 80 years or older had significantly lower odds to receive targeted therapies (EGFR or VEGF inhibitors in patients with RAS-WT tumors: adjusted odds ratio [aOR], 0.53; 95% CI, 0.36-0.79; and VEGF inhibitors in patients with RAS-Mut tumors: aOR, 0.62; 95% CI, 0.42-0.90). Improved survival was associated with EGFR inhibitor therapy in patients with RAS-WT tumors (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.74-0.98). Unlike in clinical trials, however, no survival benefit was noted with use of VEGF inhibitors among patients with RAS-WT (aHR, 1.00; 95% CI, 0.91-1.11) or RAS-Mut (aHR, 1.01; 95% CI, 0.93-1.10) tumors. CONCLUSIONS AND RELEVANCE: The findings of this study showed mixed results on survival benefits associated with targeted therapy. In addition, given that some of the results differed from those of randomized clinical trials, this study highlights the importance of using data originating from routine clinical care. American Medical Association 2023-01-19 /pmc/articles/PMC9857024/ /pubmed/36656585 http://dx.doi.org/10.1001/jamanetworkopen.2022.50030 Text en Copyright 2023 Koroukian SM et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Koroukian, Siran M.
Booker, Benjamin D.
Vu, Long
Schumacher, Fredrick R.
Rose, Johnie
Cooper, Gregory S.
Selfridge, J. Eva
Markt, Sarah C.
Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer
title Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer
title_full Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer
title_fullStr Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer
title_full_unstemmed Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer
title_short Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer
title_sort receipt of targeted therapy and survival outcomes in patients with metastatic colorectal cancer
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857024/
https://www.ncbi.nlm.nih.gov/pubmed/36656585
http://dx.doi.org/10.1001/jamanetworkopen.2022.50030
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