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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.

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.

SUBMITTER: Patel B

PROVIDER: S-EPMC8306284 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cetuximab remains to date the only targeted therapy approved for the treatment of head and neck squamous cell carcinoma (HNSCC). The EGFR pathway plays a key role in the tumorigenesis and progression of this disease as well as in the resistance to radiotherapy (RT). While several anti-EGFR agents have been tested in HNSCC, cetuximab, an IgG1 subclass monoclonal antibody against EGFR, is the only drug with proven efficacy for the treatment of both locoregionally-advanced (LA) and recurrent/metastatic (R/M) disease. The addition of cetuximab to radiotherapy is a validated treatment option in LA-HNSCC. However, its use has been limited to patients who are considered unfit for standard of care chemoradiotherapy (CRT) with single agent cisplatin given the lack of direct comparison of these two regimens in randomized phase III trials and the inferiority suggested by metanalysis and phase II studies. The current use of cetuximab in HNSCC is about to change given the recent results from randomized prospective clinical trials in both the LA and R/M setting. Two phase III studies evaluating RT-cetuximab vs. CRT in Human Papillomavirus (HPV)-positive LA oropharyngeal squamous cell carcinoma (De-ESCALaTE and RTOG 1016) showed inferior overall survival and progression-free survival for RT-cetuximab combination, and therefore CRT with cisplatin remains the standard of care in this disease. In the R/M HNSCC, the EXTREME regimen has been the standard of care as first-line treatment for the past 10 years. However, the results from the KEYNOTE-048 study will likely position the anti-PD-1 agent pembrolizumab as the new first line treatment either alone or in combination with chemotherapy in this setting based on PD-L1 status. Interestingly, cetuximab-mediated immunogenicity through antibody dependent cell cytotoxicity (ADCC) has encouraged the evaluation of combined approaches with immune-checkpoint inhibitors in both LA and R/M-HNSCC settings. This article reviews the accumulated evidence on the role of cetuximab in HNSCC in the past decade, offering an overview of its current impact in the treatment of LA and R/M-HNSCC disease and its potential use in the era of immunotherapy.

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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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