What is the management of metastatic oropharyngeal squamous cell carcinoma (SCC)?

From the Guidelines

Management of metastatic oropharyngeal squamous cell carcinoma (SCC) typically involves a multidisciplinary approach with systemic therapy as the backbone, and first-line treatment usually consists of platinum-based chemotherapy combined with cetuximab or pembrolizumab, depending on PD-L1 status. For PD-L1 positive tumors (Combined Positive Score ≥1), pembrolizumab plus platinum (cisplatin 100 mg/m² or carboplatin AUC 5) and 5-fluorouracil (1000 mg/m²) every 3 weeks for 6 cycles, followed by pembrolizumab maintenance (200 mg every 3 weeks) for up to 2 years is recommended, as shown in the KEYNOTE-048 study 1. For PD-L1 negative tumors, the EXTREME regimen is often used: cisplatin (100 mg/m²) or carboplatin (AUC 5) on day 1,5-fluorouracil (1000 mg/m²/day) as continuous infusion on days 1-4, and cetuximab (initial dose 400 mg/m², then 250 mg/m² weekly) for 6 cycles, followed by cetuximab maintenance.

The following key points should be considered in the management of metastatic oropharyngeal SCC:

• PD-L1 status is crucial in determining the first-line treatment, with pembrolizumab plus platinum/5-FU being the preferred option for PD-L1 positive tumors 1.
• The EXTREME regimen is a viable alternative for PD-L1 negative tumors, with cisplatin or carboplatin, 5-fluorouracil, and cetuximab being used for 6 cycles, followed by cetuximab maintenance 1.
• HPV status is important for prognostic purposes but does not currently alter treatment selection.
• Local therapies, including stereotactic radiotherapy or surgical resection, may be considered for patients with oligometastatic disease, in addition to systemic therapy 1.
• Second-line options include single-agent immunotherapy, such as nivolumab or pembrolizumab, especially for those who haven't received immunotherapy previously 1.
• Supportive care, including pain management, nutritional support, and psychosocial services, is essential throughout treatment, with regular imaging assessments (typically CT or PET/CT every 2-3 months) to evaluate treatment response 1.

In terms of specific treatment regimens, the following options are available:

• Pembrolizumab monotherapy for PD-L1 positive tumors 1.
• Pembrolizumab plus platinum/5-FU for PD-L1 positive tumors 1.
• The EXTREME regimen (cisplatin or carboplatin, 5-fluorouracil, and cetuximac) for PD-L1 negative tumors 1.
• Nivolumab or pembrolizumab as second-line options for patients who have not received immunotherapy previously 1.

It is essential to note that the treatment of metastatic oropharyngeal SCC should be individualized, taking into account the patient's PD-L1 status, HPV status, and overall health, as well as the presence of any comorbidities or contraindications to specific treatments, as recommended by the ehns-esmo-estro clinical practice guidelines for diagnosis, treatment and follow-up 1.

From the FDA Drug Label

The efficacy of KEYTRUDA was investigated in KEYNOTE-048 (NCT02358031), a randomized, multicenter, open-label, active-controlled trial conducted in 882 patients with metastatic HNSCC who had not previously received systemic therapy for metastatic disease or with recurrent disease who were considered incurable by local therapies.

The trial demonstrated a statistically significant improvement in OS for patients randomized to KEYTRUDA in combination with chemotherapy compared to those randomized to cetuximab in combination with chemotherapy at a pre-specified interim analysis in the overall population.

The management of oropharyngeal SCC metastatic disease may involve the use of pembrolizumab (KEYTRUDA) in combination with chemotherapy, as it has shown a statistically significant improvement in overall survival (OS) compared to chemotherapy alone or cetuximab in combination with chemotherapy in patients with metastatic head and neck squamous cell cancer (HNSCC). Key points include:

• OS: Median OS was 13.0 months (95% CI: 10.9,14.7) for patients treated with KEYTRUDA in combination with chemotherapy.
• PFS: Median PFS was 4.9 months (95% CI: 4.7,6.0) for patients treated with KEYTRUDA in combination with chemotherapy.
• ORR: The objective response rate was 36% (95% CI: 30.0,41.5) for patients treated with KEYTRUDA in combination with chemotherapy.
• Duration of Response: The median duration of response was 6.7 months (range: 1.6+, 30.4+) for patients treated with KEYTRUDA in combination with chemotherapy. 2

From the Research

Oropharyngeal SCC Metastatic Management

• The management of oropharyngeal squamous cell carcinoma (OPSCC) involves various treatment options, including surgery, radiation therapy, and chemotherapy 3.
• For recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), the combination of pembrolizumab and cetuximab has shown promising clinical activity, with an overall response rate of 45% 4.
• The addition of docetaxel to the combination of cisplatin, fluorouracil, and cetuximab did not improve efficacy in patients with recurrent and/or metastatic SCCHN, and was associated with increased toxicity 5.
• For patients ineligible for cisplatin-based chemotherapy, the weekly regimen of paclitaxel, carboplatin, and cetuximab has been shown to be an interesting option, with favorable progression-free survival and overall survival rates 6.
• Radiation therapy plays a crucial role in the management of OPSCC, and the use of concurrent high-dose intermittent cisplatin with definitive radiation therapy is recommended for patients with stage IV and stage T3 N0-1 OPSCC 7.

Treatment Options

• Surgery: may be used for early-stage OPSCC, with the goal of preserving organ function and achieving optimal cosmetic results 3.
• Radiation therapy: may be used as definitive treatment for OPSCC, or as adjuvant treatment following surgical resection 7.
• Chemotherapy: may be used in combination with radiation therapy, or as a single agent for recurrent or metastatic disease 4, 5, 6.
• Immunotherapy: pembrolizumab, a PD-1 inhibitor, has shown promising clinical activity in combination with cetuximab for recurrent or metastatic HNSCC 4.

Future Directions

• Further research is needed to optimize treatment outcomes for patients with OPSCC, including the development of new therapeutic agents and the refinement of existing treatment strategies 4, 5, 6, 7.
• The use of biomarkers and molecular profiling may help to identify patients who are most likely to benefit from specific treatments, and to develop personalized treatment plans 3.