Targeted Oncology

, Volume 13, Issue 5, pp 567–582 | Cite as

Treatment of Advanced Merkel Cell Carcinoma: Current Therapeutic Options and Novel Immunotherapy Approaches

  • Daniela Femia
  • Natalie Prinzi
  • Andrea Anichini
  • Roberta Mortarini
  • Federico Nichetti
  • Francesca Corti
  • Martina Torchio
  • Giorgia Peverelli
  • Filippo Pagani
  • Andrea Maurichi
  • Ilaria Mattavelli
  • Massimo Milione
  • Nice Bedini
  • Ambra Corti
  • Maria Di Bartolomeo
  • Filippo de Braud
  • Sara PuscedduEmail author
Review Article


Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches. Biological and genome sequencing studies have implicated multiple molecular pathways in MCC, thus leading to the development of new agents that target angiogenic factors, anti-apoptosis molecules, poly-ADP ribose polymerase, intracellular signal proteins such as the PI3K/AKT/mTOR pathway, and peptide receptors such as somatostatin receptors. More recently, immunotherapy agents such as avelumab, pembrolizumab, and nivolumab, which act by blocking the programmed cell-death (PD)-1/PD-L1 immune checkpoint, have shown promising results, especially in the advanced setting, and should now be considered standard of care for metastatic MCC. Current research is focusing on developing new immunotherapeutic strategies, identifying predictive biomarker to aid in the selection of patients responsive to immunotherapy, and defining combination approaches to increase efficacy in refractory patients.



Editorial assistance in the preparation of this manuscript was provided by Aashni Shah, on behalf of Polistudium (Milan, Italy); this assistance was supported by internal funds. We also thank Lilia Biscaglia, PhD, for useful discussion.

Compliance with Ethical Standards


No external funding was used in the preparation of this manuscript.

Conflict of Interest

Daniela Femia, Natalie Prinzi, Andrea Anichini, Roberta Mortarini, Federico Nichetti, Francesca Corti, Martina Torchio, Giorgia Peverelli, Filippo Pagani, Andrea Maurichi, Ilaria Mattavelli, Massimo Milione, Nice Bedini, Ambra Corti, Maria Di Bartolomeo, Filippo de Braud, and Sara Pusceddu declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Daniela Femia
    • 1
  • Natalie Prinzi
    • 1
  • Andrea Anichini
    • 2
  • Roberta Mortarini
    • 2
  • Federico Nichetti
    • 1
  • Francesca Corti
    • 1
  • Martina Torchio
    • 1
  • Giorgia Peverelli
    • 1
  • Filippo Pagani
    • 1
  • Andrea Maurichi
    • 3
  • Ilaria Mattavelli
    • 3
  • Massimo Milione
    • 4
  • Nice Bedini
    • 5
  • Ambra Corti
    • 6
  • Maria Di Bartolomeo
    • 1
  • Filippo de Braud
    • 1
    • 7
  • Sara Pusceddu
    • 1
    Email author
  1. 1.Department of Medical Oncology Unit-1Fondazione IRCCS Istituto Nazionale dei Tumori di Milano and ENETS Center of ExcellenceMilanItaly
  2. 2.Department of Research, Human Tumors Immunobiology UnitFondazione IRCCS Istituto Nazionale dei Tumori, Milano and ENETS Center of ExcellenceMilanItaly
  3. 3.Melanoma and Sarcoma UnitFondazione IRCCS Istituto Nazionale dei Tumori, ENETS Center of ExcellenceMilanItaly
  4. 4.1st Pathology Division, Department of Pathology and Laboratory MedicineFondazione IRCCS Istituto Nazionale dei Tumori and ENETS Center of ExcellenceMilanItaly
  5. 5.Radiation Oncology 1Fondazione IRCCS Istituto Nazionale dei Tumori, Milano and ENETS Center of ExcellenceMilanItaly
  6. 6.PolistudiumMilanItaly
  7. 7.University of MilanMilanItaly

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