Medication Summary

In 2017, avelumab became the first drug approved by the FDA for metastatic Merkel cell carcinoma in adults and children aged 12 years or older. It is a programmed death 1 (PD-1) inhibitor.^[20]In 2018, another PD-1 inhibitor, pembrolizumab, was approved for adults and children with metastatic or recurrent, locally advanced Merkel cell carcinoma.^{[22, 21]} Retifanlimab, approved in March 2023, is the most recent PD-1 inhibitor approved.^[23]

Platinum-based chemotherapy regimens have been also been used, but clinical efficacy is limited and brief.

Class Summary

Programmed cell death-1 (PD-1) and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells under normal conditions. PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound.

This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation.

Avelumab (Bavencio)

View full drug information

Anti-PD-L1 IgG1 monoclonal antibody. It is indicated for metastatic MCC in adults and pediatric patients aged 12 years or older.

Pembrolizumab (Keytruda)

View full drug information

Monoclonal antibody that targets PD-1. It blocks PD-1 from interacting with ligands PD-L1 and PD-L2. Indicated for adults and children with metastatic or recurrent, locally advanced Merkel cell carcinoma.

Retifanlimab (Zynyz)

View full drug information

Indicated for adults with metastatic or recurrent, locally advanced Merkel cell carcinoma.

Questions

Brady M, Spiker AM. Cancer, Skin, Merkel Cell. StatPearls. 2018 Jan. [QxMD MEDLINE Link]. [Full Text].
Muller-Richter UDA, Gesierich A, Kubler AC, Hartmann S, Brands RC. Merkel Cell Carcinoma of the Head and Neck: Recommendations for Diagnostics and Treatment. Ann Surg Oncol. 2017 Oct. 24 (11):3430-7. [QxMD MEDLINE Link]. [Full Text].
Kim JA, Choi AH. Effect of radiation therapy on survival in patients with resected Merkel cell carcinoma: a propensity score surveillance, epidemiology, and end results database analysis. JAMA Dermatol. 2013 Jul. 149(7):831-8. [QxMD MEDLINE Link].
Lebbe C, Becker JC, Grob JJ, et al. Diagnosis and treatment of Merkel cell carcinoma. European consensus-based interdisciplinary guideline. Eur J Cancer. 2015 Aug 6. [QxMD MEDLINE Link].
Mayo Clinic. Merkel cell carcinoma. Available at https://www.mayoclinic.org/diseases-conditions/merkel-cell-carcinoma/symptoms-causes/syc-20351030. Accessed: 2019 Jul 22.
Cleveland Clinic. Merkel cell carcinoma: prevention. Available at https://my.clevelandclinic.org/health/diseases/17971-merkel-cell-carcinoma/prevention. Reviewed 2019 Jan 11; Accessed: 2019 Jul 22.
Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972 Jan. 105(1):107-10. [QxMD MEDLINE Link].
Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. 2005 Jan 1. 89(1):1-4. [QxMD MEDLINE Link].
Uitentuis SE, Louwman MWJ, van Akkooi ACJ, Bekkenk M. Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands. J Am Acad Dermatol. 2019 Jan 28. [QxMD MEDLINE Link].
Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008 Feb 22. 319(5866):1096-100. [QxMD MEDLINE Link]. [Full Text].
Busam KJ, Jungbluth AA, Rekthman N, et al. Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Pathol. 2009 Sep. 33(9):1378-85. [QxMD MEDLINE Link]. [Full Text].
Xie H, Lee L, Caramuta S, Höög A, Browaldh N, Björnhagen V, et al. MicroRNA Expression Patterns Related to Merkel Cell Polyomavirus Infection in Human Merkel Cell Carcinoma. J Invest Dermatol. 2013 Aug 20. [QxMD MEDLINE Link].
Kwun HJ, Shuda M, Feng H, Camacho CJ, Moore PS, Chang Y. Merkel cell polyomavirus small T antigen controls viral replication and oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7. Cell Host Microbe. 2013 Aug 14. 14(2):125-35. [QxMD MEDLINE Link]. [Full Text].
Faust H, Andersson K, Ekström J, Hortlund M, Robsahm TE, Dillner J. Prospective study of Merkel cell polyomavirus and risk of Merkel cell carcinoma. Int J Cancer. 2013 Aug 7. [QxMD MEDLINE Link].
Yao M, Smith RB, Hoffman HT, et al. Merkel cell carcinoma: two case reports focusing on the role of fluorodeoxyglucose positron emission tomography imaging in staging and surveillance. Am J Clin Oncol. 2005 Apr. 28(2):205-10. [QxMD MEDLINE Link].
Gould VE, Moll R, Moll I, et al. Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest. 1985 Apr. 52(4):334-53. [QxMD MEDLINE Link].
Yiengpruksawan A, Coit DG, Thaler HT, et al. Merkel cell carcinoma. Prognosis and management. Arch Surg. 1991 Dec. 126(12):1514-9. [QxMD MEDLINE Link].
Bishop AJ, Garden AS, Gunn GB, et al. Merkel cell carcinoma of the head and neck: Favorable outcomes with radiotherapy. Head Neck. 2015 Feb 2. [QxMD MEDLINE Link].
Chen MM, Roman SA, Sosa JA, Judson BL. The role of adjuvant therapy in the management of head and neck Merkel cell carcinoma: an analysis of 4815 patients. JAMA Otolaryngol Head Neck Surg. 2015 Feb. 141 (2):137-41. [QxMD MEDLINE Link].
Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016 Oct. 17 (10):1374-1385. [QxMD MEDLINE Link].
FDA. FDA approves pembrolizumab for Merkel cell carcinoma. US Food and Drug Administration. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm628867.htm. 2018 Dec 19; Accessed: 2018 Dec 20.
Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. N Engl J Med. 2016 Jun 30. 374 (26):2542-52. [QxMD MEDLINE Link]. [Full Text].
Grignani G, Rutkowski P, Lebbe C, et al. 545 A phase 2 study of retifanlimab in patients with advanced or metastatic Merkel cell carcinoma (MCC) (POD1UM-201). J Immunother Cancer. 2021. 9 (Suppl 2):[Full Text].
Perez MC, de Pinho FR, Holstein A, et al. Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?. Ann Surg Oncol. 2018 Oct. 25 (11):3334-40. [QxMD MEDLINE Link].
Papadiochos I, Patrikidou A, Patsatsi A, Mangoudi D, Thuau H, Vahtsevanos K. Head and neck Merkel cell carcinoma: a retrospective case series and critical literature review with emphasis on treatment and prognosis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018 Feb. 125 (2):126-39. [QxMD MEDLINE Link].
Silva EG, Mackay B, Goepfert H, et al. Endocrine carcinoma of the skin (Merkel cell carcinoma). Pathol Annu. 1984. 19 Pt 2:1-30. [QxMD MEDLINE Link].
Cotlar AM, Gates JO, Gibbs FA Jr. Merkel cell carcinoma: combined surgery and radiation therapy. Am Surg. 1986 Mar. 52(3):159-64. [QxMD MEDLINE Link].
Goepfert H, Remmler D, Silva E, et al. Merkel cell carcinoma (endocrine carcinoma of the skin) of the head and neck. Arch Otolaryngol. 1984 Nov. 110(11):707-12. [QxMD MEDLINE Link].
Hitchcock CL, Bland KI, Laney RG 3d, et al. Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment. Ann Surg. 1988 Feb. 207(2):201-7. [QxMD MEDLINE Link].
Fields RC, Busam KJ, Chou JF, et al. Five hundred patients with merkel cell carcinoma evaluated at a single institution. Ann Surg. 2011 Sep. 254(3):465-75. [QxMD MEDLINE Link].
O'Connor WJ, Roenigk RK, Brodland DG. Merkel cell carcinoma. Comparison of Mohs micrographic surgery and wide excision in eighty-six patients. Dermatol Surg. 1997 Oct. 23(10):929-33. [QxMD MEDLINE Link].
Schmalbach CE, Lowe L, Teknos TN, et al. Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma. Arch Otolaryngol Head Neck Surg. 2005 Jul. 131(7):610-4. [QxMD MEDLINE Link].

Media Gallery

Common distribution of Merkel cell carcinoma in the head and neck.
Merkel cell carcinoma affecting the right nasal ala.

of 2

Author

James M Pearson, MD Private Practice, Beverly Hills/Hermosa Beach, CA

James M Pearson, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, California Medical Association, Los Angeles County Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Michael J Pitman, MD Associate Professor of Otolaryngology-Head and Neck Surgery, Columbia University College of Physicians and Surgeons; Chief, Division of Laryngology, Director, Voice and Swallowing Institute, ColumbiaDoctors, Columbia University Medical Center

Michael J Pitman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, Voice Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

M Sherif Said, MD, PhD Associate Professor, Department of Pathology, University of Colorado School of Medicine; Associate Director of Pathology Department, Denver Health Medical Center

M Sherif Said, MD, PhD is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan; Ryte; Neosoma; MI10<br/>Received income in an amount equal to or greater than $250 from: Neosoma; Cyberionix (CYBX)<br/>Received ownership interest from Cerescan for consulting for: Neosoma, MI10.

Additional Contributors

M Abraham Kuriakose, MD, DDS, FRCS Chairman, Head and Neck Institute, Amrita Institute of Medical Sciences

M Abraham Kuriakose, MD, DDS, FRCS is a member of the following medical societies: American Association for Cancer Research, American Head and Neck Society, British Association of Oral and Maxillofacial Surgeons, Royal College of Surgeons of England

Disclosure: Nothing to disclose.