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. 2017 May;66(5):573-579. doi: 10.1007/s00262-017-1960-8. Epub 2017 Feb 14.

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.

Keywords: ADCC; Cetuximab; EGFR; Head and neck cancer; Outcome.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody-Dependent Cell Cytotoxicity
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Line, Tumor
  • Cetuximab / therapeutic use*
  • Chemoradiotherapy
  • ErbB Receptors / metabolism*
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Squamous Cell Carcinoma of Head and Neck
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab