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Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis

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Abstract

Background

The addition of monoclonal antibodies targeting the epidermal growth factor receptor (anti-EGFR Abs) to chemotherapy for metastatic colorectal carcinoma (mCRC) is commonly delayed in the real-world clinical practice, usually because of late RAS testing results.

Objective

To determine whether delayed addition of anti-EGFR mAbs up to the fourth cycle of backbone chemotherapy adversely affected outcomes of mCRC patients treated with first-line regimens.

Patients and Methods

Clinical data of patients with histologically verified, RAS wild-type mCRC treated with first-line systemic therapy regimens containing anti-EGFR mAbs were retrospectively analysed from a national database. Patients were divided into three groups according to the timing of anti-EGFR mAbs addition to the chemotherapy backbone. Cohort A (n = 401) included patients in whom anti-EGFR mAbs were added to chemotherapy from the first cycle, cohort B (n = 71) patients with anti-EGFR mAbs added to chemotherapy from the second cycle, and cohort C (n = 101) patients who had anti-EGFR mAbs added to chemotherapy from the third or fourth cycle.

Results

Three hundred and thirty-six (58.6%) patients received panitumumab and 237 (41.4%) patients received cetuximab. The median progression-free survival (PFS) of the whole cohort was 12.2 months (95% confidence interval [CI] 10.9–13.5), and the median overall survival (OS) was 33.5 months (95% CI 27.6–39.4). The median PFS and OS for patients treated with anti-EGFR mAbs added to chemotherapy were 12.9 (95% CI 11.5–14.3) and 30.6 months (95% CI 25.2–36.1) for cohort A, 9.7 (95% CI 9.1–10.3) and not reached for cohort B, compared to 11.5 (95% CI 9.8–13.2) and 37.9 months (95% CI 28.6–47.3) for cohort C, respectively.

Conclusions

Delayed addition of anti-EGFR mAbs to first-line chemotherapy was not associated with inferior survival or response rates.

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Acknowledgments

We would like to thank the following heads of the comprehensive cancer centres for the permission to use data of patients from their respective regional networks: Dr. Martina Chodacka, Chomutov Hospital and Masaryk Hospital in Usti nad Labem; Dr. Vaclav Janovsky, Ceske Budejovice Hospital; Dr. Otakar Bednarik, University Hospital, Brno; Dr. Jana Prausova, Motol University Hospital, Prague; Dr. David Feltl, University Hospital, Ostrava; Professor Jiri Petera, University Hospital, Hradec Kralove; Dr. Jana Katolicka, St Anna University Hospital, Brno; Professor Rostislav Vyzula, Masaryk Memorial Institute of Oncology, Brno; Dr. Jiri Bartos, County Hospital, Liberec; Dr. Martin Safanda, Na Homolce Hospital, Prague; Dr. Renata Soumarova, Novy Jicin Hospital; Professor Jitka Abrahamova, Thomayer Hospital, Prague. We are also indebted to all physicians who provided data for the CORECT registry.

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Author notes

  1. Ondrej Fiala and Veronika Veskrnova contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, University Hospital, Svobody 80, 304 60, Pilsen, Czech Republic

    Ondrej Fiala & Jindrich Finek

  2. Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic

    Ondrej Fiala

  3. Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Videnska 800, 140 59, Prague, Czech Republic

    Veronika Veskrnova, Ludmila Boubliková, Josef Dvorak & Tomas Buchler

  4. Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Netroufalky 5, 625 00, Brno, Czech Republic

    Renata Chloupkova & Ladislav Dusek

  5. Department of Comprehensive Cancer Care and Faculty of Medicine, Masaryk Memorial Cancer Institute and Masaryk University, Zluty kopec 543/7, 656 53, Brno, Czech Republic

    Alexandr Poprach, Igor Kiss & Marek Svoboda

  6. Department of Oncology, Motol University Hospital and Second Faculty of Medicine, Charles University, V Uvalu 84, 150 00, Prague, Czech Republic

    Katerina Kopeckova

  7. Department of Oncology, Jihlava Hospital Comprehensive Cancer Centre, Jihlava, Czech Republic

    Lubomir Slavicek

  8. Department of Oncology, T Bata Hospital and Comprehensive Cancer Centre, Zlin, Czech Republic

    Milan Kohoutek

  9. Department of Oncology, General University Hospital and Charles University First Faculty of Medicine, U Nemocnice 499/2, 128 08, Prague, Czech Republic

    Lubos Petruzelka

  10. Department of Oncology, Palacky University Medical School and Teaching Hospital, I.P. Pavlova 6, 775 20, Olomouc, Czech Republic

    Bohuslav Melichar

Authors
  1. Ondrej Fiala
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  2. Veronika Veskrnova
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  3. Renata Chloupkova
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  5. Igor Kiss
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  6. Katerina Kopeckova
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  9. Milan Kohoutek
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  13. Ludmila Boubliková
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  16. Tomas Buchler
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Corresponding author

Correspondence to Tomas Buchler.

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Funding

This study was supported by grants AZV 15-26535A from the Czech Health Research Council, “Center of Clinical and Experimental Liver Surgery”, UNCE/MED/006, and the National Sustainability Program I (NPU I) Nr. LO1503 from the Ministry of Education Youth and Sports of the Czech Republic.

Conflict of Interest

T. Buchler, and B. Melichar have received research funding, travel grants, and honoraria from Roche, Merck, Bayer, Servier, BMS, MSD, Sanofi, and Amgen. O. Fiala received honoraria from Roche, Merck, and Amgen. J. Finek has received consulting fees and lecture honoraria from Roche, Bayer, BMS, Sanofi, Pierre Fabre, and Amgen. M. Svoboda received consulting fees from Amgen. V. Veskrnova, R. Chloupkova, K. Kopeckova, I. Kiss, L. Dusek, L. Slavicek, M. Kohoutek, A. Poprach, L. Petruzelka, L. Boublikova, and J. Dvorak declare no conflict of interest that might be relevant to the contents of the manuscript.

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Fiala, O., Veskrnova, V., Chloupkova, R. et al. Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis. Targ Oncol 13, 735–743 (2018). https://doi.org/10.1007/s11523-018-0597-7

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