What line of therapy is carboplatin, fluorouracil (5-FU), and cetuximab (Erbitux) for a patient with sarcomatoid squamous cell carcinoma of the retromolar trigone according to NCCN guidelines?

First-Line Therapy According to NCCN Guidelines

The carboplatin, fluorouracil (5-FU), and cetuximab regimen represents first-line systemic therapy for recurrent/metastatic squamous cell carcinoma of the retromolar trigone according to NCCN guidelines. 1

Guideline-Recommended First-Line Regimens

The NCCN guidelines for head and neck cancers explicitly designate the following as Category 1 first-line treatment options for recurrent and/or metastatic squamous cell carcinoma of the head and neck (which includes retromolar trigone): 1

• Cisplatin or carboplatin plus 5-FU with cetuximab (for non-nasopharyngeal cancer only) - This is the EXTREME regimen, which demonstrated improved median survival (10.1 vs 7.4 months, P=0.04) and response rate (36% vs 20%, P<0.001) compared to platinum/5-FU alone 1

• Alternative first-line combinations include cisplatin or carboplatin plus a taxane, or cisplatin with cetuximab (for non-nasopharyngeal cancer only) 1

Updated Treatment Landscape

While the EXTREME regimen (platinum/5-FU/cetuximab) has been the standard first-line therapy for over a decade, more recent EHNS-ESMO-ESTRO 2020 guidelines have updated recommendations based on the KEYNOTE-048 trial: 1

• For PD-L1-positive tumors with no platinum-based chemotherapy in the last 6 months: Pembrolizumab monotherapy is now standard [I, A] 1

• For PD-L1-negative tumors with no platinum-based chemotherapy in the last 6 months: Pembrolizumab plus platinum/5-FU is standard [I, A] 1

• Platinum/5-FU/cetuximab remains standard [I, A] for patients pretreated with platinum-based chemotherapy within the last 6 months and who are immunotherapy-naïve 1

Clinical Context for Your Patient

For a patient with sarcomatoid squamous cell carcinoma of the retromolar trigone receiving carboplatin/5-FU/cetuximab: 1

• This represents first-line systemic therapy if the patient has recurrent or metastatic disease not amenable to curative surgery or radiation 1

• The regimen is appropriate for patients with good performance status (PS 0-1) who are fit for platinum-based therapy 1

• Combination regimens like this typically double response rates compared to single agents, though they come with increased toxicity requiring close monitoring by an experienced multidisciplinary team 1

Important Treatment Considerations

All combined chemoradiotherapy and systemic therapy regimens for head and neck cancer are associated with significant mucosal toxicities requiring close monitoring 1

The cetuximab component requires: 2

• Weekly monitoring of serum electrolytes (magnesium, potassium, calcium) during and for at least 8 weeks after treatment completion
• Monitoring for dermatologic toxicities, particularly acneiform rash (occurs in 82% of patients, severe in 10%)
• Careful consideration in patients with history of coronary artery disease, congestive heart failure, or arrhythmias when combined with platinum-based therapy

Median survival with first-line chemotherapy for metastatic head and neck cancer is approximately 10-11 months with the EXTREME regimen, with 1-year survival rates around 40% 1