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Elevated basal antibody-dependent cell-mediated cytotoxicity (ADCC) and high epidermal growth factor receptor (EGFR) expression predict favourable outcome in patients with locally advanced head and neck cancer treated with cetuximab and radiotherapy

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Abstract

Background

Antibody-dependent cell-mediated cytotoxicity (ADCC) may contribute to the antitumor activity of cetuximab. However, the extent of this contribution is unclear. In this study, we investigated the impact of baseline ADCC on the outcome of patients with locally advanced squamous cell carcinoma treated with cetuximab and radiotherapy.

Methods

We determined baseline ADCC in 28 patients treated with cetuximab and radiotherapy and in 15 patients treated with chemoradiation. We linked the values observed with complete response and with overall survival. We also considered the role of epidermal growth factor receptor (EGFR) expression and studied the combined effect of EGFR and ADCC.

Results

We observed a wide range of baseline values of ADCC. Complete response did not correlate with either ADCC or EGFR expression. However, when ADCC and EGFR were considered together using a mixed score, they significantly correlated with achieving a complete response (p = 0.04). High baseline ADCC significantly correlated with outcome compared to low (p = 0.03), but not in patients treated without cetuximab. Patients showing high baseline levels of both ADCC and EGFR3+ achieved the best outcome compared to the others (p = 0.02).

Conclusions

In this study, patients treated with cetuximab and radiotherapy, showing high baseline of both ADCC and EGFR3+, have significant higher probability of achieving a complete response and a long overall survival compared to the others.

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Abbreviations

ADCC:

Antibody-dependent cell-mediated cytotoxicity

CR:

Complete response

IgG:

Immunoglobulin G

INFγ:

Interferon gamma

iNKT:

Invariant natural killer T cells

mAbs:

Monoclonal antibodies

N:

Lymph node status

OPC:

Oropharyngeal cancers

pts:

Patients

T:

Tumor size

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Acknowledgements

This study has been partially supported by Associazione Ricerca Clinica Oncologica (ARCO) Foundation, Cuneo, Italy.

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Authors and Affiliations

  1. Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, via Carle 25, 12100, Cuneo, Italy

    Laura Lattanzio, Daniela Vivenza, Chiara Varamo, Martino Monteverde, Cristiana Lo Nigro & Marco Merlano

  2. Medical Oncology, Oncology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy

    Nerina Denaro & Marco Merlano

  3. Pathology Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy

    Giuliana Strola, Mirella Fortunato & Alberto Comino

  4. Oncopharmacology Unit, Centre A. Lacassagne, Nice, France

    Emmanuel Chamorey & Gerard Milano

Authors
  1. Laura Lattanzio
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  2. Nerina Denaro
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  3. Daniela Vivenza
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  4. Chiara Varamo
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  5. Giuliana Strola
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  6. Mirella Fortunato
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  7. Emmanuel Chamorey
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  8. Alberto Comino
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  9. Martino Monteverde
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  10. Cristiana Lo Nigro
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  11. Gerard Milano
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  12. Marco Merlano
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Corresponding author

Correspondence to Laura Lattanzio.

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Conflict of interest

Marco Merlano took part in Merck Serono and MSD advisory boards, and has speaker role in Merck Serono promoted meetings. All other authors declare no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Lattanzio, L., Denaro, N., Vivenza, D. et al. Elevated basal antibody-dependent cell-mediated cytotoxicity (ADCC) and high epidermal growth factor receptor (EGFR) expression predict favourable outcome in patients with locally advanced head and neck cancer treated with cetuximab and radiotherapy. Cancer Immunol Immunother 66, 573–579 (2017). https://doi.org/10.1007/s00262-017-1960-8

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  • DOI: https://doi.org/10.1007/s00262-017-1960-8

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