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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
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Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance

Nabil F. Saba, Zhuo Gerogia Chen, Missak Haigentz, Paolo Bossi, Alessandra Rinaldo, Juan P. Rodrigo, Antti A. Mäkitie, Robert P. Takes, Primoz Strojan, Jan B. Vermorken and Alfio Ferlito
Nabil F. Saba
1Department of Hematology and Medical oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
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  • For correspondence: nfsaba@emory.edu
Zhuo Gerogia Chen
1Department of Hematology and Medical oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
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Missak Haigentz
2Atlantic Health System, Morristown, New Jersey.
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  • ORCID record for Missak Haigentz
Paolo Bossi
3Medical Oncology Department, University of Brescia, Brescia, Italy.
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Alessandra Rinaldo
4University of Udine School of Medicine, Udine, Italy.
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Juan P. Rodrigo
5Hospital Universitario Central de Asturias, Oviedo, Spain.
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  • ORCID record for Juan P. Rodrigo
Antti A. Mäkitie
6Department of Otorhinolaryngology–Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland.
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  • ORCID record for Antti A. Mäkitie
Robert P. Takes
7Radboud University Medical Center, Nijmegen, the Netherlands.
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Primoz Strojan
8Institute of Oncology, Ljubljana, Slovenia.
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Jan B. Vermorken
9Antwerp University Hospital, Edegem, Belgium.
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Alfio Ferlito
10Coordinator of the International Head and Neck Scientific Group, Padua, Italy.
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DOI: 10.1158/1535-7163.MCT-19-0214 Published November 2019
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    Figure 1.

    Resistant mechanisms of EGFR-targeted therapy. The following molecular activities will result in bypassing EGFR blockade: (A) Activation mutations or amplification of EGFR downstream signaling effectors; (B) Overexpression of MET proto-oncogene and expression of EGFR variant III; (C) Heterodimerization between EGFR family members; and (D) Activation of TGFβ–IL6 axis.

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    Ongoing and published clinical trials combining EGFR monoclonal antibodies with immunotherapeutic agents in SCCHN

    DesignTitleTrial numberStatus
    Phase IIA Phase I/II Study of Concurrent Cetuximab and Nivolumab in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell CarcinomaNCT03370276Recurrent or metastatic
    Phase IIIRandomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)NCT02999087Locoregional
    Phase III (terminated)Nivolumab or Nivolumab Plus Cisplatin or Cetuximab, in Combination with Radiotherapy in Patients with Cisplatin-ineligible or Eligible Locally Advanced Squamous Cell Head and Neck CancerNCT03349710Locoregional
    Phase IPhase I trial of cetuximab, intensity modulated radiotherapy (IMRT), and the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab in previously untreated, locally advanced head and neck squamous cell carcinoma (PULA HNSCC)NCT 0193592Locoregional
    Phase IIMotolimod and Standard Combination Chemotherapy with Cetuximab in Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck: The Active8 Randomized Clinical Trial.NCT01836029Recurrent and metastatic SCCHN (manuscript published; ref. 88).
    Phase IIEACH: Evaluating Avelumab in Combination with Cetuximab in Head and Neck Cancer (EACH)NCT03494322Locoregional
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Molecular Cancer Therapeutics: 18 (11)
November 2019
Volume 18, Issue 11
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Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance
Nabil F. Saba, Zhuo Gerogia Chen, Missak Haigentz, Paolo Bossi, Alessandra Rinaldo, Juan P. Rodrigo, Antti A. Mäkitie, Robert P. Takes, Primoz Strojan, Jan B. Vermorken and Alfio Ferlito
Mol Cancer Ther November 1 2019 (18) (11) 1909-1915; DOI: 10.1158/1535-7163.MCT-19-0214

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Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance
Nabil F. Saba, Zhuo Gerogia Chen, Missak Haigentz, Paolo Bossi, Alessandra Rinaldo, Juan P. Rodrigo, Antti A. Mäkitie, Robert P. Takes, Primoz Strojan, Jan B. Vermorken and Alfio Ferlito
Mol Cancer Ther November 1 2019 (18) (11) 1909-1915; DOI: 10.1158/1535-7163.MCT-19-0214
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    • Rationale for Inhibiting EGFR in SCCHN
    • The Limitations of Anti-EGFR Targeting in SCCHN
    • Resistance Mechanisms to EGFR Inhibition
    • Emergence of Immunotherapy as an Effective Therapeutic Modality in SCCHN
    • Immune Implications of EGFR Targeting
    • Forging the Alliance
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Molecular Cancer Therapeutics
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