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Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

Authors Buchler T, Chloupkova R, Poprach A, Fiala O, Kiss I, Kopeckova K, Dusek L, Veskrnova V, Slavicek L, Kohoutek M, Finek J, Svoboda M, Petruzelka L, Melichar B

Received 8 August 2018

Accepted for publication 7 December 2018

Published 28 December 2018 Volume 2019:11 Pages 359—368

DOI https://doi.org/10.2147/CMAR.S183093

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 4

Editor who approved publication: Dr Kenan Onel


Tomas Buchler,1 Renata Chloupkova,2 Alexandr Poprach,3 Ondrej Fiala,4,5 Igor Kiss,3 Katerina Kopeckova,6 Ladislav Dusek,2 Veronika Veskrnova,1 Lubomir Slavicek,7 Milan Kohoutek,8 Jindrich Finek,4 Marek Svoboda,3 Lubos Petruzelka,9 Bohuslav Melichar10

1Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, 140 59 Prague, Czech Republic; 2Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic; 3Department of Comprehensive Cancer Care and Faculty of Medicine, Masaryk Memorial Cancer Institute and Masaryk University, Brno 656 53, Czech Republic; 4Department of Oncology, University Hospital, 304 60 Pilsen, Czech Republic; 5Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic; 6Department of Oncology, Motol University Hospital and Second Faculty of Medicine, Charles University, 150 00 Prague, Czech Republic; 7Department of Oncology, Jihlava Hospital Comprehensive Cancer Centre, Jihlava, Czech Republic; 8Department of Oncology, T Bata Hospital and Comprehensive Cancer Centre, Zlin, Czech Republic; 9Department of Oncology, General University Hospital and Charles University First Faculty of Medicine, 128 08 Prague, Czech Republic; 10Department of Oncology, Palacky University Medical School and Teaching Hospital, 775 20 Olomouc, Czech Republic

Purpose: Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear.
Methods: A national registry of targeted therapies was used to analyze baseline ­characteristics and outcomes of patients with mCRC and wild-type KRAS exon 2 status who received ­bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first- and second-line ­treatment in either sequence.
Results: The cohort included 490 patients (181 patients treated with first-line EGFRi and second-line bevacizumab and 309 patients treated with first-line bevacizumab and second-line EGFRi). Median overall survival (OS) from the initiation on first-line therapy was similar for patients treated with either sequence, reaching 31.8 (95% CI 27.5–36.1) vs 31.4 months (95% CI 27.8–35.0) for EGFRi → bevacizumab vs bevacizumab → EGFRi cohort, respectively. Time from first-line initiation to progression on the second-line therapy [progression-free survival (PFS)] was 21.1 (95% CI 19.3–23.0) vs 19.3 months (95% CI 17.3–21.3) for bevacizumab → EGFRi vs EGFRi → bevacizumab cohort, respectively (P=0.016).
Conclusion: This retrospective analysis of real-world data of patients with wild-type KRAS exon 2 mCRC showed no differences in OS between cohorts treated with bevacizumab → EGFRi vs the reverse sequence while combined PFS favored the bevacizumab → EGFRi sequence.

Keywords: colorectal carcinoma, bevacizumab, panitumumab, cetuximab, sequence

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