What is the treatment approach for stage IV Merkel cell carcinoma?

Treatment Approach for Stage IV Merkel Cell Carcinoma

Immune checkpoint inhibitors, particularly avelumab, should be used as first-line systemic therapy for stage IV Merkel cell carcinoma due to their durable response rates compared to chemotherapy. 1

First-Line Treatment Options

Immunotherapy

• Avelumab is FDA-approved for metastatic MCC in adults and pediatric patients 12 years and older 2
• Pembrolizumab is FDA-approved for recurrent locally advanced or metastatic MCC 3
• These immune checkpoint inhibitors provide response rates similar to chemotherapy but with potentially greater durability of response 1
• Real-world data shows improved median overall survival with immunotherapy (16.2 months) compared to chemotherapy (12.3 months) or no systemic therapy (8.7 months) 4

For Patients with Contraindications to Immunotherapy

If immunotherapy is contraindicated or after progression on immunotherapy, consider:

• Platinum-based chemotherapy regimens:
  • Cisplatin ± etoposide
  • Carboplatin ± etoposide 5, 1
• Alternative chemotherapy options:
  • Topotecan (particularly in older patients)
  • Cyclophosphamide + doxorubicin + vincristine (CAV) - note this regimen has significant toxicity 5

Multidisciplinary Management

1. Comprehensive Imaging:

   • Full imaging workup (CT, MRI, or PET/CT) is recommended for all patients with metastatic disease 5
   • PET-CT is the most sensitive staging modality and can reveal clinically occult disease in approximately 16% of patients 6

2. Multidisciplinary Tumor Board Consultation:

   • Required for all patients with metastatic disease to consider all treatment options 5
   • Treatment should be individually tailored based on disease extent and patient factors 5

3. Local Treatment Options for Oligometastatic Disease:

   • Surgery may be beneficial for select patients with oligometastasis 5
   • Radiation therapy can be considered for symptomatic lesions 1
   • Combining radiation therapy with immunotherapy may lead to complete clinical regression in some patients 1, 7

Safety Considerations and Monitoring

• Immune-related adverse events require close monitoring, with common side effects including thyroiditis and hypothyroidism 1
• Chemotherapy carries toxic death rates of 3-10%, with elderly patients at higher risk 1
• First-line chemotherapy may have response rates up to 70%, but responses are typically short-lived (2-9 months) 1
• Response rates drop to 9-20% in subsequent lines of chemotherapy 1

Follow-Up Recommendations

• Physical examination including complete skin and regional lymph node examination every 3-6 months for first 2 years, then every 6-12 months thereafter 5
• Imaging studies should be performed as clinically indicated, with routine imaging considered for high-risk patients 5
• Blood-based surveillance tests (Merkel cell polyomavirus antibodies and circulating tumor DNA) can be considered as they show excellent sensitivity 6
• 90% of recurrences occur within 24 months, with median time to recurrence being approximately 8 months 5

Clinical Pearls and Pitfalls

• Treatment at high-volume centers is associated with improved overall survival (HR=0.58) and increased likelihood of receiving appropriate first-line immunotherapy 4
• Clinical trial participation should be encouraged whenever available and appropriate 5
• Best supportive care should be provided to all patients, with the goal of maximizing quality of life while extending survival 1
• MCC is a rare disease that precludes robust randomized studies, so treatment decisions may need to be made based on limited evidence 5
• The major clinical challenge is managing ICI-refractory disease, which requires consideration of alternative approaches 6