Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

doi:10.3390/cancers13143545

Review

. 2021 Jul 15;13(14):3545.

doi: 10.3390/cancers13143545.

Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

Bhamini Patel¹, Nabil F Saba²

Affiliations

¹ Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
² Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.

PMID: 34298761
PMCID: PMC8306284
DOI: 10.3390/cancers13143545

Review

Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

Bhamini Patel et al. Cancers (Basel). 2021.

. 2021 Jul 15;13(14):3545.

doi: 10.3390/cancers13143545.

Authors

Bhamini Patel¹, Nabil F Saba²

Affiliations

¹ Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
² Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.

PMID: 34298761
PMCID: PMC8306284
DOI: 10.3390/cancers13143545

Abstract

Recurrent metastatic (RM) and locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) are devasting disease states with limited therapeutic options and poor overall survival. Targeting the epidermal growth factor receptor (EGFR) is one area that has helped improve outcomes in this disease. Anti-EGFR based therapies have been shown to improve overall survival and mitigate the significant toxicities incurred from standard radiation, chemotherapy, and/or surgical options. Cetuximab, the most well-studied anti-EGFR monoclonal antibody, has demonstrated a positive impact on outcomes for RM and LA SCCHN. However, the development of early resistance to cetuximab highlights the need for a wider arsenal of therapy for RM and LA diseases. The use of immune checkpoint inhibitors has recently transformed the treatment of recurrent SCCHN. Drugs such as pembrolizumab and nivolumab have demonstrated success in recent clinical trials and have been approved for the treatment of advanced disease. Given the positive results of both EGFR targeted agents and immune checkpoint inhibitors, ongoing trials are studying their synergistic effects.

Keywords: EGFR and chemotherapy in SCCHN; EGFR inhibition in head and neck cancer; EGFR monoclonal antibodies; Epidermal Growth Factor and squamous cell carcinoma; combination immunotherapy and EGFR in head and neck cancer; head and neck squamous cell carcinoma; pembrolizumab and monoclonal antibody in SCCHN.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
This figure represents potential resistance mechanisms to EGFR inhibition. (A) Activation mutations or amplifications of downstream EGFR pathways; (B) Overexpression of MET protooncogene and expression of EGFR variant III; (C) Heterodimerization between other RTK family members; (D) Activation of TGFβ-IL6 axis. Reused from: Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance [9].

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References

1. Santuray R.T., Johnson D.E., Grandis J.R. New Therapies in Head and Neck Cancer. Trends Cancer. 2018;4:385–396. doi: 10.1016/j.trecan.2018.03.006. - DOI - PMC - PubMed
1. Zimmermann M., Zouhair A., Azria D., Ozsahin M. The epidermal growth factor receptor (EGFR) in head and neck cancer: Its role and treatment implications. Radiat. Oncol. 2006;1:11. doi: 10.1186/1748-717X-1-11. - DOI - PMC - PubMed
1. Xu M.J., Johnson D.E., Grandis J.R. EGFR-targeted therapies in the post-genomic era. Cancer Metastasis Rev. 2017;36:463–473. doi: 10.1007/s10555-017-9687-8. - DOI - PMC - PubMed
1. Juergens R.A., Bratman S.V., Tsao M.-S., Laurie S.A., Kuruvilla M.S., Razak A.R.A., Hansen A.R. Biology and patterns of response to EGFR-inhibition in squamous cell cancers of the lung and head & neck. Cancer Treat. Rev. 2017;54:43–57. doi: 10.1016/j.ctrv.2017.01.003. - DOI - PubMed
1. Vigneswara V., Kong A. Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN) Ann. Oncol. 2018;29:794–796. doi: 10.1093/annonc/mdy065. - DOI - PubMed

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[1] Santuray R.T., Johnson D.E., Grandis J.R. New Therapies in Head and Neck Cancer. Trends Cancer. 2018;4:385–396. doi: 10.1016/j.trecan.2018.03.006. - DOI - PMC - PubMed

[2] Santuray R.T., Johnson D.E., Grandis J.R. New Therapies in Head and Neck Cancer. Trends Cancer. 2018;4:385–396. doi: 10.1016/j.trecan.2018.03.006. - DOI - PMC - PubMed

[3] Zimmermann M., Zouhair A., Azria D., Ozsahin M. The epidermal growth factor receptor (EGFR) in head and neck cancer: Its role and treatment implications. Radiat. Oncol. 2006;1:11. doi: 10.1186/1748-717X-1-11. - DOI - PMC - PubMed

[4] Zimmermann M., Zouhair A., Azria D., Ozsahin M. The epidermal growth factor receptor (EGFR) in head and neck cancer: Its role and treatment implications. Radiat. Oncol. 2006;1:11. doi: 10.1186/1748-717X-1-11. - DOI - PMC - PubMed

[5] Xu M.J., Johnson D.E., Grandis J.R. EGFR-targeted therapies in the post-genomic era. Cancer Metastasis Rev. 2017;36:463–473. doi: 10.1007/s10555-017-9687-8. - DOI - PMC - PubMed

[6] Xu M.J., Johnson D.E., Grandis J.R. EGFR-targeted therapies in the post-genomic era. Cancer Metastasis Rev. 2017;36:463–473. doi: 10.1007/s10555-017-9687-8. - DOI - PMC - PubMed

[7] Juergens R.A., Bratman S.V., Tsao M.-S., Laurie S.A., Kuruvilla M.S., Razak A.R.A., Hansen A.R. Biology and patterns of response to EGFR-inhibition in squamous cell cancers of the lung and head & neck. Cancer Treat. Rev. 2017;54:43–57. doi: 10.1016/j.ctrv.2017.01.003. - DOI - PubMed

[8] Juergens R.A., Bratman S.V., Tsao M.-S., Laurie S.A., Kuruvilla M.S., Razak A.R.A., Hansen A.R. Biology and patterns of response to EGFR-inhibition in squamous cell cancers of the lung and head & neck. Cancer Treat. Rev. 2017;54:43–57. doi: 10.1016/j.ctrv.2017.01.003. - DOI - PubMed

[9] Vigneswara V., Kong A. Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN) Ann. Oncol. 2018;29:794–796. doi: 10.1093/annonc/mdy065. - DOI - PubMed

[10] Vigneswara V., Kong A. Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN) Ann. Oncol. 2018;29:794–796. doi: 10.1093/annonc/mdy065. - DOI - PubMed

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Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

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Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

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