What is the treatment for squamous cell carcinoma (SCC) of the head and neck?

From the Guidelines

The treatment for squamous cell carcinoma (SCC) of the head and neck typically involves a multidisciplinary approach based on the stage, location, and patient factors, with the most recent and highest quality study 1 guiding the use of immunotherapy and biomarker testing in recurrent and metastatic head and neck cancers.

Overview of SCC of the Head and Neck

Squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 4% of all cancers in the United States, with an estimated 66,470 new diagnoses and 15,050 deaths in 2022, as reported in 1. The crude incidence of SCCHN in the European Union is 34.6/100 000/year, with a mortality rate of 13.7/100 000/year, according to 1. More than 90% of head and neck malignancies are squamous cell carcinomas.

Diagnosis and Staging

Pathologic diagnosis should be made according to the WHO classification from a surgical biopsy sample, as recommended in 1. Routine staging includes physical examination, chest X-ray, head and neck endoscopy, and head and neck CT scan or MRI. A thoracic CT scan may be carried out to rule out metastatic disease. Squamous cell head and neck cancer should be staged according to the TNM system and grouped into the following categories.

Treatment Approach

• Early-stage disease: Often treated with surgery or radiation therapy alone. For surgery, complete tumor resection with negative margins is the goal, sometimes requiring reconstruction. Radiation therapy typically involves 60-70 Gy delivered over 6-7 weeks.
• Locally advanced disease: Combined modality treatment is standard, including surgery followed by adjuvant radiation or chemoradiation, or definitive chemoradiation. The standard chemotherapy regimen during radiation is cisplatin (100 mg/m² every 3 weeks or 40 mg/m² weekly), as supported by 1 and 1.
• Recurrent or metastatic disease: Options include pembrolizumab (200 mg every 3 weeks) alone for PD-L1 positive tumors or combined with platinum/5-FU chemotherapy, or the EXTREME regimen (platinum, 5-FU, and cetuximab), as discussed in 1 and 1.

Considerations and Supportive Care

Treatment decisions should consider functional outcomes and quality of life, as head and neck cancer therapy can affect critical functions like speech and swallowing. Supportive care, including nutritional support, speech therapy, and dental care, is essential throughout treatment. The approach is personalized based on tumor characteristics, patient performance status, and comorbidities to balance cancer control with preservation of function.

Key considerations for managing cisplatin-ineligible patients with resected, high-risk, locally advanced squamous cell carcinoma of the head and neck are discussed in 1, emphasizing the need for alternative systemic therapy options in combination with radiotherapy.

Follow-up care, as outlined in 1 and 1, should include regular physical examinations, radiologic imaging, and evaluation of thyroid function in patients with irradiation to the neck, to detect potentially curable locoregional recurrence and second tumors early.

From the FDA Drug Label

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Squamous cell carcinoma of the head and neck is a type of cancer that can be treated with pembrolizumab (KEYTRUDA). The treatment options include:

• Combination therapy: KEYTRUDA with platinum and fluorouracil (FU) for first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC)
• Single agent: KEYTRUDA for first-line treatment of patients with metastatic or unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1)
• Single agent: KEYTRUDA for treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy 2

From the Research

Definition of Squamous Cell Carcinoma of the Head and Neck

• Squamous cell carcinoma (SCC) of the head and neck is a complex cancer that requires a multidisciplinary approach for treatment 3.
• It is a type of cancer that originates in the squamous cells, which are the flat, thin cells that make up the outer layer of the skin and lining of some organs 3.

Treatment Options for Squamous Cell Carcinoma of the Head and Neck

• For patients with locally or regionally advanced disease, surgery and/or radiation are the cornerstones of definitive treatment 3.
• Medical therapy plays an important adjunct role in this setting, typically consisting of a platinum-based regimen given as induction, concurrent, or adjuvant treatment 3.
• Chemotherapy regimens such as carboplatin, fluorouracil, and methotrexate have been used as initial treatment in patients with locally advanced head and neck cancer 4.
• Concurrent chemoradiation with carboplatin and radiation has been shown to be a highly active and well-tolerated regimen for untreated patients with inoperable squamous cell carcinoma of the head and neck 5.
• Neoadjuvant chemotherapy, which is chemotherapy given before the main treatment, has been revisited as an option for locally advanced SCCHN, with the cisplatin-fluorouracil combination being superseded by a combination of cisplatin, fluorouracil, and a taxane 6.
• For patients with recurrent or metastatic head and neck squamous cell carcinoma who are unfit for the standard EXTREME schedule, carboplatin in combination with weekly paclitaxel has been shown to be an effective and tolerable first-line therapy 7.

Treatment Outcomes and Toxicities

• The overall response rate to chemotherapy regimens such as carboplatin, fluorouracil, and methotrexate has been reported to be around 40-50% 4, 7.
• The median progression-free survival and overall survival have been reported to be around 4-6 months and 8-12 months, respectively 4, 7.
• Common toxicities associated with chemotherapy regimens include myelosuppression, nausea, vomiting, stomatitis, and diarrhea 5, 4, 7.
• The addition of carboplatin to radiation therapy has been shown to not increase the rate of surgical complications over that expected for preoperative radiotherapy 5.