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Previous Bevacizumab and Efficacy of Later Anti–Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry

  • Matthew Burge
    Correspondence
    Address for correspondence: Matthew Burge, MBChB, FRACP, Royal Brisbane and Women’s Hospital, Brisbane, Queensland 4029, Australia
    Affiliations
    Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia

    University of Queensland, St Lucia, Brisbane, Queensland, Australia
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  • Christine Semira
    Affiliations
    Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia
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  • Belinda Lee
    Affiliations
    Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia

    Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia

    Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
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  • Margaret Lee
    Affiliations
    Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia

    Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia

    Department of Medical Oncology, Western Health, St Albans, Victoria, Australia

    Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
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  • Suzanne Kosmider
    Affiliations
    Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
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  • Rachel Wong
    Affiliations
    Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia

    Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
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  • Jeremy Shapiro
    Affiliations
    Department of Medical Oncology, Cabrini Health, Malvern, Victoria, Australia

    Department of Medicine, Monash University, Clayton, Victoria, Australia
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  • Brigette Ma
    Affiliations
    Department of Clinical Oncology, Chinese University of Hong Kong, New Territories, Hong Kong
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  • Andrew P. Dean
    Affiliations
    Department of Medical Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia
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  • Allan S. Zimet
    Affiliations
    Department of Medical Oncology, Epworth Hospital, Richmond, Victoria, Australia
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  • Simone A. Steel
    Affiliations
    Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
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  • Sheau Wen Lok
    Affiliations
    Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia

    Victoriatorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
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  • Javier Torres
    Affiliations
    Department of Medical Oncology, Goulburn Valley Health, Shepparton, Victoria, Australia
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  • Melissa Eastgate
    Affiliations
    Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia

    University of Queensland, St Lucia, Brisbane, Queensland, Australia
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  • Hui-li Wong
    Affiliations
    Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia

    Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia

    Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
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  • Peter Gibbs
    Affiliations
    Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia

    Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia

    Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia

    Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
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      Abstract

      Background

      The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis.

      Materials and Methods

      We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use.

      Results

      Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was < 6 versus > 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26).

      Conclusion

      Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.

      Keywords

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