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

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Medical Oncology Unit-1, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano and ENETS Center of Excellence, Via Venezian 1, 20133, Milan, Italy

    Daniela Femia, Natalie Prinzi, Federico Nichetti, Francesca Corti, Martina Torchio, Giorgia Peverelli, Filippo Pagani, Maria Di Bartolomeo, Filippo de Braud & Sara Pusceddu

  2. Department of Research, Human Tumors Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano and ENETS Center of Excellence, Milan, Italy

    Andrea Anichini & Roberta Mortarini

  3. Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, ENETS Center of Excellence, Milan, Italy

    Andrea Maurichi & Ilaria Mattavelli

  4. 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori and ENETS Center of Excellence, Milan, Italy

    Massimo Milione

  5. Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano and ENETS Center of Excellence, Milan, Italy

    Nice Bedini

  6. Polistudium, Milan, Italy

    Ambra Corti

  7. University of Milan, Milan, Italy

    Filippo de Braud

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  1. Daniela Femia
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Correspondence to Sara Pusceddu.

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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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Femia, D., Prinzi, N., Anichini, A. et al. Treatment of Advanced Merkel Cell Carcinoma: Current Therapeutic Options and Novel Immunotherapy Approaches. Targ Oncol 13, 567–582 (2018). https://doi.org/10.1007/s11523-018-0585-y

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