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Metastatic Merkel Cell Carcinoma: Treatment Challenges and Best Practices With Paul Nghiem, MD, PhD

Paul T. Nghiem, MD, PhD

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of unknown origin that typically presents in older white and immunocompromised adults. An estimated 1,500 cases are diagnosed in the United States annually. The rapid rise of MCC incidence during the past few decades has been attributed in part to people living longer with increased sun exposure and weakened immune systems, a feature that suggests an infectious origin and warrants further research. Treatment standards are lacking and consequently clinical decision making is often empirical rather than evidence-based. The mortality rate for MCC presently exceeds that of melanoma. The overall 5-year survival rate ranges from 30% to 64%. In this interview, Paul T. Nghiem, MD, PhD, professor of dermatology/medicine at the University of Washington School of Medicine, shares insights into current challenges, best practices, and promising advances in the management of metastatic MCC.

What are some of the most challenging aspects of managing metastatic MCC?

Paul T. Nghiem, MD, PhD: About half of patients with metastatic MCC will benefit persistently from immune therapy (via PD1 pathway blockade), while the other half will not. Sometimes, continuing immune therapy and adding palliative radiation can help them. Other times, we add a CTLA-4­–based checkpoint inhibitor, or switch them to palliative chemotherapy for a little while. Now, the greatest challenge is to figure out how we can help people who are refractory to immunotherapy.

What are best practices that you would recommend to community oncologists who are managing metastatic MCC?

Dr. Nghiem: If a patient has advanced MCC and no contraindications for immune therapy, treatment with a PD1 pathway blocking agent is likely indicated. For trickier circumstances, it might be helpful to work with a regional cancer center with a multi-disciplinary, active MCC-focused group.

When these patients are referred to you, where do you see room for improvement?

Dr. Nghiem: Multi-disciplinary consultation is the most important thing that should have happened. Were radiation, surgery, and medical approaches properly considered to minimize toxicity and maximize efficacy & quality of life?

What questions do you commonly encounter from patients about their treatment and how do you counsel them?

Dr. Nghiem: Patients always want to know their chances of success (a bit over 50%) and risks of side effects (fatigue in about half, and significant auto-immune side effects in about 20%). I provide them with a list of possible auto-immune side effects and a card for their wallet/purse to explain that they are not on 'chemotherapy' but are getting immune therapy. Side effects can thus be extremely varied and challenging to recognize.

What are some promising advances in metastatic MCC treatment that you expect to see in the near future (targeted therapy, immunotherapy, etc.)?

Dr. Nghiem: We hope to know how immune therapy fits into adjuvant therapy for MCC. Hopefully, we'll also figure out how to help people with disease that is refractory to single-agent immune therapy.

Is there anything else you'd like to add for community oncologists treating metastatic MCC?

Dr. Nghiem: I encourage them to become familiar with the antibody test for the virus, which can help them identify recurrent disease very sensitively. It can spare scans in many cases and can be extremely reassuring to patients that their cancer is not returning. This validated blood test is described in the NCCN (National Comprehensive Cancer Network) guidelines and at this website: www.merkelcell.org/sero

About Dr. Nghiem

Paul Nghiem, MD, PhD is the George F. Odland Chair in Dermatology, Head of Dermatology, and professor of dermatology/medicine at the University of Washington School of Medicine. Dr. Nghiem oversees a laboratory focused on the biology of skin cancer, managing several clinical studies of its genetic mechanisms and optimal clinical management of patients. Merkel cell carcinoma has been a major focus of his clinical work and research. Among his many involvements in professional organizations and publications, Dr. Nghiem has served on the editorial board of the Journal of the American Academy of Dermatology for several years. In 2014, he was also elected as a member of the American Society for Clinical Investigation, which recognizes physicians whose research has had an impact on the understanding and treatment of disease.

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