Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancer

Abstract Purpose Combination of biological therapy and chemotherapy improves the survival of patients with metastatic colorectal cancer (mCRC). However, the optimal biological therapy sequence remains unclear. In this retrospective study, we evaluated the clinical outcomes of patients with mCRC trea...

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Main Authors: Hung‐Chih Hsu, Yu‐Chun Liu, Chuang‐Wei Wang, Wen-Chi Chou, Yu-Jen Hsu, Jy-Ming Chiang, Yung-Chang Lin, Tsai-Sheng Yang
Format: Article
Language:English
Published: Wiley 2019-07-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.2235
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author Hung‐Chih Hsu
Yu‐Chun Liu
Chuang‐Wei Wang
Wen-Chi Chou
Yu-Jen Hsu
Jy-Ming Chiang
Yung-Chang Lin
Tsai-Sheng Yang
author_facet Hung‐Chih Hsu
Yu‐Chun Liu
Chuang‐Wei Wang
Wen-Chi Chou
Yu-Jen Hsu
Jy-Ming Chiang
Yung-Chang Lin
Tsai-Sheng Yang
author_sort Hung‐Chih Hsu
collection DOAJ
description Abstract Purpose Combination of biological therapy and chemotherapy improves the survival of patients with metastatic colorectal cancer (mCRC). However, the optimal biological therapy sequence remains unclear. In this retrospective study, we evaluated the clinical outcomes of patients with mCRC treated with different sequences of biological therapies as first‐ and third‐line therapy. Methods We only included patients with wild‐type KRAS exon 2 mCRC who had received cetuximab, bevacizumab, and standard chemotherapy. The patients were treated with cetuximab or bevacizumab as first‐ or third‐line therapy combined with a similar chemotherapy backbone. Results In total, 102 patients were included. Forty‐six patients received first‐line cetuximab therapy followed by third‐line bevacizumab therapy (cetuximab → bevacizumab group) and 56 patients received first‐line bevacizumab therapy followed by third‐line cetuximab therapy (bevacizumab → cetuximab group). The cetuximab → bevacizumab group was associated with increased survival (OS) compared with the bevacizumab → cetuximab group (median OS: 30.4 months vs 25.7 months, hazard ratio (HR): 0.55, 95% confidence interval (CI): 0.36‐0.86). When calculated from the start of second‐ and third‐line therapies, OS was also higher in the cetuximab → bevacizumab group (second‐line: 20.6 months vs 14.8 months, HR: 0.54, 95% CI: 0.34‐0.81; third‐line: 12.5 months vs 9.9 months, HR: 0.53, 95% CI: 0.35‐0.83). The cetuximab → bevacizumab group was also associated with better progression‐free survival than the bevacizumab → cetuximab group (8.8 vs 4.5 months, HR: 0.43, 95% CI: 0.25‐0.58) in the third‐line setting, but not in the first‐ or second‐line settings. Conclusions Our study demonstrated that first‐line cetuximab therapy followed by third‐line bevacizumab therapy was associated with favorable clinical outcomes as compared to the reverse sequence.
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spelling doaj.art-66d815ddf4d5467198a4d00f0ed001b92022-12-22T01:56:57ZengWileyCancer Medicine2045-76342019-07-01873437344610.1002/cam4.2235Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancerHung‐Chih Hsu0Yu‐Chun Liu1Chuang‐Wei Wang2Wen-Chi Chou3Yu-Jen Hsu4Jy-Ming Chiang5Yung-Chang Lin6Tsai-Sheng Yang7Division of Hematology‑Oncology Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanCollege of Medicine Chang Gung University Taoyuan TaiwanDepartment of Dermatology, Drug Hypersensitivity Clinical and Research Center Chang Gung Memorial Hospitals Taipei TaiwanDivision of Hematology‑Oncology Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanCollege of Medicine Chang Gung University Taoyuan TaiwanCollege of Medicine Chang Gung University Taoyuan TaiwanDivision of Hematology‑Oncology Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanDivision of Hematology‑Oncology Chang Gung Memorial Hospital at Linkou Taoyuan TaiwanAbstract Purpose Combination of biological therapy and chemotherapy improves the survival of patients with metastatic colorectal cancer (mCRC). However, the optimal biological therapy sequence remains unclear. In this retrospective study, we evaluated the clinical outcomes of patients with mCRC treated with different sequences of biological therapies as first‐ and third‐line therapy. Methods We only included patients with wild‐type KRAS exon 2 mCRC who had received cetuximab, bevacizumab, and standard chemotherapy. The patients were treated with cetuximab or bevacizumab as first‐ or third‐line therapy combined with a similar chemotherapy backbone. Results In total, 102 patients were included. Forty‐six patients received first‐line cetuximab therapy followed by third‐line bevacizumab therapy (cetuximab → bevacizumab group) and 56 patients received first‐line bevacizumab therapy followed by third‐line cetuximab therapy (bevacizumab → cetuximab group). The cetuximab → bevacizumab group was associated with increased survival (OS) compared with the bevacizumab → cetuximab group (median OS: 30.4 months vs 25.7 months, hazard ratio (HR): 0.55, 95% confidence interval (CI): 0.36‐0.86). When calculated from the start of second‐ and third‐line therapies, OS was also higher in the cetuximab → bevacizumab group (second‐line: 20.6 months vs 14.8 months, HR: 0.54, 95% CI: 0.34‐0.81; third‐line: 12.5 months vs 9.9 months, HR: 0.53, 95% CI: 0.35‐0.83). The cetuximab → bevacizumab group was also associated with better progression‐free survival than the bevacizumab → cetuximab group (8.8 vs 4.5 months, HR: 0.43, 95% CI: 0.25‐0.58) in the third‐line setting, but not in the first‐ or second‐line settings. Conclusions Our study demonstrated that first‐line cetuximab therapy followed by third‐line bevacizumab therapy was associated with favorable clinical outcomes as compared to the reverse sequence.https://doi.org/10.1002/cam4.2235anti‐EGFR/anti‐VEGFbiological therapy sequencemetastatic colorectal cancersurvival
spellingShingle Hung‐Chih Hsu
Yu‐Chun Liu
Chuang‐Wei Wang
Wen-Chi Chou
Yu-Jen Hsu
Jy-Ming Chiang
Yung-Chang Lin
Tsai-Sheng Yang
Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancer
Cancer Medicine
anti‐EGFR/anti‐VEGF
biological therapy sequence
metastatic colorectal cancer
survival
title Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancer
title_full Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancer
title_fullStr Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancer
title_full_unstemmed Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancer
title_short Sequential cetuximab/bevacizumab therapy is associated with improved outcomes in patients with wild‐type KRAS exon 2 metastatic colorectal cancer
title_sort sequential cetuximab bevacizumab therapy is associated with improved outcomes in patients with wild type kras exon 2 metastatic colorectal cancer
topic anti‐EGFR/anti‐VEGF
biological therapy sequence
metastatic colorectal cancer
survival
url https://doi.org/10.1002/cam4.2235
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