Abstract: Squamous cell carcinoma of the head and neck (SCCHN) is the most common head and neck tumor, with higher disease burden. More than 90% SCCHN patients with overexpression of epidermal growth factor receptor (EGFR). Therefore, one important method to inhibit EGFR signaling is through the specific high affinity binding of monoclonal antibody to EGFR. Among a variety of current drugs targeting EGFR and its pathway, cetuximab is the only targeted drug with definite efficacy and has been approved in China since February 2020 for the first-line treatment of recurrent/metastatic SCCHN (R/M SCCHN). With the gradual clinical application of cetuximab, the overall treatment model for patients with advanced SCCHN in China will continue to be improved and optimized. It is worth noting that although targeted and immune drugs have made great progress in the treatment of SCCHN, there are still many challenges. Consensus has not yet been reached for cetuximab on EGFR detection, drug application timing, combination regimen and suitable dosage, and adverse reaction management in the treatment of R/M SCCHN. This expert consensus has combined the literature and clinical practice in China to explain the efficacy and safety of cetuximab in first-line, second-line and combined immunotherapy of R/M SCCHN, and provides relevant recommendations regarding treatment strategies. It is hoped that this consensus will provide guidance for the standardized treatment of SCCHN patients with cetuximab and the optimization of clinical practice. After several rounds of discussion, experts of the consensus group have provided the following recommendations. In terms of molecular testing, patients with R/M SCCHN do not need routine testing of EGFR to inform clinical practice. Anti-EGFR monoclonal antibodies exert anti-tumor effect by inhibiting EGFR signaling. In first-line treatment, 6 cycles of cetuximab in combination with cisplatin 75 mg/m ² and 5-FU 750 mg/m ² are recommended for platinum-tolerant patients, followed with cetuximab maintenance monotherapy after disease response or stable disease until progressive disease; 4 cycles of cetuximab in combination with platinum (cisplatin 75 mg/m ² , q3w) + docetaxel (75 mg/m ² , q3w) are recommended for patients with contraindications to 5-FU, inconvenience with continuous intravenous infusion, dihydropyrimidine dehydrogenase (DPD) deficiency and poor treatment compliance, followed with cetuximab maintenance monotherapy after disease response or stable disease until progressive disease; cetuximab in combination with paclitaxel weekly is recommended for platinum-intolerant patients until progressive disease; and cetuximab maintenance monotherapy is recommended for elderly patients in good condition after 6 cycles of cetuximab + carboplatin + 5-FU. Multiple clinical studies and real-world data have shown consistent high objective response rate (ORR) and survival benefit with cetuximab in combination with chemotherapy in first-line treatment. In second-line treatment, for patients who have failed first-line platinum-based chemotherapy, weekly treatment with cetuximab monotherapy or in combination with paclitaxel is recommended; for patients who have failed first-line immune checkpoint inhibitor (ICI) treatment, cetuximab in combination with chemotherapy is recommended, and the combined drugs should be adjusted based on previous drug exposure. In terms of safety, the most common adverse events related to cetuximab treatment include skin reaction, infusion reaction and electrolyte disturbance. Most skin reactions are mild and manageable with precautions and generally will resolve without sequelae upon discontinuation or dose reduction of cetuximab. Infusion reactions can be effectively controlled by precautions before infusion, close monitoring during and after infusion and timely intervention. Adverse reactions associated with cetuximab treatment are generally well tolerated and acceptable compared with those associated with chemotherapy alone. In addition, the use of cetuximab in combination with immunotherapy or new targeted drugs is explored and will bring more possibilities for R/M SCCHN patients in the future.

Key words: Epidermal growth factor receptor, Anti-epidermal growth factor receptor antibody, Recurrent/metastatic squamous cell carcinoma of the head and neck, Consensus, Targeted therapy