What are the current treatments for head and neck squamous cell carcinoma (HNSCC)?

From the Guidelines

The current treatment of head and neck squamous cell carcinoma (HNSCC) involves a multidisciplinary approach tailored to disease stage, location, and patient factors, with a focus on combined modality treatment for locally advanced disease, including surgery followed by adjuvant radiation with or without chemotherapy, or definitive chemoradiation, as recommended by the most recent study 1.

Treatment Approach

For early-stage disease (stages I-II), single-modality treatment with either surgery or radiation therapy is typically recommended, with 5-year survival rates of 70-90%.

• The standard concurrent chemotherapy regimen is high-dose cisplatin (100 mg/m² every 3 weeks for 3 cycles), though weekly cisplatin (40 mg/m²) may be used for patients unable to tolerate the high-dose regimen.
• For recurrent or metastatic disease, treatment options include immunotherapy with pembrolizumab (200 mg IV every 3 weeks) either alone or in combination with platinum-based chemotherapy, depending on PD-L1 expression.
• EGFR inhibitors like cetuximab may be added to radiation or used in recurrent disease, as shown in a recent study 1.

Supportive Care

Supportive care addressing nutrition, speech, swallowing, and psychosocial needs is essential throughout treatment to maintain quality of life and optimize outcomes.

• Treatment advances include de-escalation strategies for HPV-positive oropharyngeal cancer, which has better prognosis, and intensification approaches for high-risk disease.
• The optimal approach to post-treatment surveillance of patients with SCCHN is still under discussion, but physical examination along with radiologic imaging should be included in the follow-up, as recommended by 1.

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.

The current treatment of head and neck squamous cell cancer includes pembrolizumab (KEYTRUDA) as a:

• first-line treatment in combination with platinum and fluorouracil (FU) for metastatic or unresectable, recurrent HNSCC
• first-line treatment as a single agent for metastatic or unresectable, recurrent HNSCC with PD-L1 expression (CPS ≥1)
• treatment as a single agent for recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy 2

From the Research

Current Treatment of Head and Neck Squamous Cell Cancer

• The current treatment of head and neck squamous cell cancer (HNSCC) involves a multidisciplinary approach, with surgery and/or radiation being the cornerstones of definitive treatment for patients with locally or regionally advanced disease 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.
• For relapsed/metastatic HNSCC, options have improved with the incorporation of biologics and immune checkpoint inhibitors, although clinical trials are ongoing to investigate novel approaches 3.

Systemic Therapy in HNSCC Treatment

• Systemic therapy, including chemotherapy and targeted agents, is used in combination or in sequence with radiation and/or surgery for cure and/or organ preservation in patients with locally advanced nonmetastatic HNSCC 4.
• High-dose cisplatin is commonly used, and concomitant chemoRT has been shown to improve overall survival 4.
• Other targeted agents, such as cetuximab, have been approved for use in HNSCC, although their effectiveness is still being studied 5, 6.

Immunotherapy and Molecularly Targeted Agents

• Immunotherapeutic agents, such as interleukin therapy and immune checkpoint inhibitor blockade, are being studied for the treatment of HNSCC 6.
• Molecularly targeted agents, including inhibitors of transmembrane growth factor receptors, angiogenesis, and PI3K/AKT/mTOR and NOTCH signaling pathways, are also being investigated 6.
• Cetuximab, an epidermal growth factor receptor inhibitor, is the only targeted agent approved by the FDA for HNSCC, and it improves overall survival when combined with chemotherapy or radiation 6.

Alternative Treatment Regimens

• For patients ineligible for cisplatin-based chemotherapy, alternative regimens such as weekly paclitaxel, carboplatin, and cetuximab (PCC) have shown promising results 7.
• The PCC regimen has been shown to have sufficient efficacy and safety, with a median overall survival of 11.7 months and a disease control rate of 65% 7.