Download PDF
CC BY 4.0 · Brazilian Journal of Oncology 2019; 15: e-20190024
DOI: 10.1055/s-0044-1791935
Review Article

Updates in the Management of Merkel Cell Carcinoma

Atualizações no manejo do Carcinoma de Células de Merkel

Paulo Henrique do Amor Divino
1   Instituto do Câncer do Estado de São Paulo, Medical Oncology Division - São Paulo - São Paulo - Brazil
,
Gabriel Passos Souza
1   Instituto do Câncer do Estado de São Paulo, Medical Oncology Division - São Paulo - São Paulo - Brazil
,
Maurício Fernando Silva-Almeida Ribeiro
2   Hospital Sírio-Libanês, Oncology Center - São Paulo - São Paulo - Brazil
,
George Horta
1   Instituto do Câncer do Estado de São Paulo, Medical Oncology Division - São Paulo - São Paulo - Brazil
,
Fabíola Ambrosio Silveira-Lima
2   Hospital Sírio-Libanês, Oncology Center - São Paulo - São Paulo - Brazil
,
Alessandra Corte Real-Salgues
2   Hospital Sírio-Libanês, Oncology Center - São Paulo - São Paulo - Brazil
,
Rodrigo Ramella Munhoz
1   Instituto do Câncer do Estado de São Paulo, Medical Oncology Division - São Paulo - São Paulo - Brazil
2   Hospital Sírio-Libanês, Oncology Center - São Paulo - São Paulo - Brazil
› Author Affiliations Financial support: none to declare.
› Further Information
   Permissions and Reprints All articles of this category

ABSTRACT

Merkel cell carcinomas are rare cutaneous malignancies with neuroendocrine features that affect elderly individuals with a history of chronic sun exposure and immunosuppression. More recently, a human viral pathogen, the Merkel cell polyomavirus, has been implicated in the carcinogenesis of this disease. Its particularly aggressive biological behavior, the delay in diagnosis related to the lack of awareness, as well as the paucity of effective therapeutic modalities have historically contributed to the high lethality and dismal prognosis. Although surgery and radiation therapy remain the therapeutic pillars for patients with localized disease, the recognition of its immunogenic potential, with the consequent development and successful implementation of immune checkpoint blockade for those with advanced disease has significantly changed the treatment landscape for these patients. In this review, etiopathogenic, diagnostic and therapeutic aspects related to Merkel cell carcinomas are thoroughly addressed.

RESUMO

Carcinomas de células de Merkel são neoplasias malignas cutâneas raras com características neuroendócrinas que afetam indivíduos idosos com história de exposição solar crônica ou imunossupressão. Recentemente, um vírus humano patogênico, o poliomavírus, tem sido relacionado com a carcinogênese da doença. Seu comportamento biológico particularmente agressivo, o atraso no diagnóstico relacionado à falta de informação e a escassez de modalidades terapêuticas eficazes têm contribuído historicamente para a alta letalidade e prognóstico sombrio. Embora a cirurgia e a radioterapia continuem sendo os pilares terapêuticos para pacientes com doença localizada, o reconhecimento de seu potencial imunogênico, com o consequente desenvolvimento e implementação bem-sucedida dos inibidores do checkpoint imune para pessoas com doença avançada mudou significativamente o cenário do tratamento para esses pacientes. Nesta revisão, aspectos etiopatogênicos, diagnósticos e terapêuticos relacionados aos carcinomas de células de Merkel são minuciosamente abordados.

Keywords:

neuroendocrine tumors - polyomavirus - immunotherapy - Carcinoma - Merkel Cell

Descritores:

Merkel cell - imunnotherapy - polyomavirus (Células de Merkel - imunoterapia - poliomavírus)

AUTHOR'S CONTRIBUTION

Paulo Henrique do Amor-Divino: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing.

Gabriel Passos Souza: Collection and assembly of data, Manuscript writing.

Maurício Fernando Silva-Almeida Ribeiro: Collection and assembly of data, Data analysis and interpretation, Manuscript writing.

George Horta: Collection and assembly of data, Manuscript writing.

Fabíola Ambrosio Silveira-Lima: Data analysis and interpretation, Manuscript writing.

Alessandra Corte Real-Salgues: Data analysis and interpretation, Manuscript writing.

Rodrigo Ramella Munhoz: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing




Publication History

Received: 18 October 2019

Accepted: 28 October 2019

Article published online:
11 December 2019

© 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

Bibliographical Record
Paulo Henrique do Amor Divino, Gabriel Passos Souza, Maurício Fernando Silva-Almeida Ribeiro, George Horta, Fabíola Ambrosio Silveira-Lima, Alessandra Corte Real-Salgues, Rodrigo Ramella Munhoz. Updates in the Management of Merkel Cell Carcinoma. Brazilian Journal of Oncology 2019; 15: e-20190024.
DOI: 10.1055/s-0044-1791935
 

  • REFERENCES

  • Toker C.. Trabecular carcinoma of the skin. Arch Dermatol 1972; 105: 107-110
    Search in Google Scholar
  • Uchi H.. Merkel cell carcinoma: An update and immunotherapy. Fron. Oncol 2018; 8: 48
    Search in Google Scholar
  • Hodgson N.. Merkel cell Carcinoma: changing incidence trends. J. Surg. Oncol 2005; 89: 1-4
    Search in Google Scholar
  • Youlden DR, Soyer HP, Youl PH, Fritschi L, Baade PD.. Incidence and survival for Merkel cell carcinoma in Queensland, Australia, 1993-2010. JAMA Dermatol 2014; 150 (08) 864-872
    Search in Google Scholar
  • Lanoy E, Costagliola D, Engels EA.. Skin cancers associated with HIV infection and solid organ transplant among elderly adults. Int J Cancer 2010; 126 (07) 1724
    Search in Google Scholar
  • Paulson KG, Carter JJ, Jonhson LG. et al Antibodies to Merkel Cell Polyomavirus T Antigen Oncoproteins Reflect Tumor Burden in Merkel Cell Carcinoma Patients. Cancer Research 2010; 70 (21) 8388-8397
    Search in Google Scholar
  • Feng H, Shuda M, Chang Y, Moore PS.. Clonal integration of a Polyomavirus in human Merkel cell carcinoma. Science 2018; 319 (5866) 10961100
    Search in Google Scholar
  • Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS. et al T antigens mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci USA 2008; 42 (105) 16272-277
    Search in Google Scholar
  • Sunshine JC, Jahchan NS, Sage J, Choi J.. Are there multiple cells of origin of Merkel cell carcinoma?. Oncogene 2018; 37: 1409-1416
    Search in Google Scholar
  • Tetzlaff MT, Nagarajan P.. Update on Merkel cell carcinoma. Head and Neck Pathology 2018; 12: 31-43
    Search in Google Scholar
  • Garneski KM, Warcola AH, Feng Q, Kiviat NB, Leonard JH, Nghiem P.. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. Journal of Investigative Dermatology 2009; 129: 246-248
    Search in Google Scholar
  • Wong SQ, Waldeck K, Vergara IA, Schröder J, Madore J, Wilmott JS. et al UV- associated mutations underlie the etiology of MCV-negative Merkel cell carcinomas. Cancer Res 2015; 75 (24) 522834
    Search in Google Scholar
  • Moshiri AS, Doumani R, Yelistratova L, Blom A, Lachance K, Shinohara MM. et al Polyomavirus-negative Merkel cell carcinoma: a more agressive subtype based on analysis of 282 cases using multimodal tumor virus detection. Journal of Investigative Dermatology 2017; 137: 81927
    Search in Google Scholar
  • Goh G, Walradt T, Markarov V, Blom A, Riaz N, Doumani R. et al Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget 2015; 3 (07) 3403-3415
    Search in Google Scholar
  • Tang CK, Toker C.. Trabecular carcinoma of the skin: an ultrastructural study. Cancer 1978; 42: 2311-2321 :5<2311::AID-CNCR2820420531>3.0.CO;2-L
    Search in Google Scholar
  • Sauer CM, Haugg AM, Chteinberg E, Rennspiess D, Winnepenninckx V, Speel E-J. et al Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma. Critical Reviews in Oncology/Hematology 2017; 116: 99-105
    Search in Google Scholar
  • Kuromi T, Matsushita M, Iwasaki T, Nonaka D, Kuwamoto S, Nagata K.. Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma. Human Pathology 2017; 69: 8-14
    Search in Google Scholar
  • Sihto H, Kukko H, Koljonen V, Sankila R, Böhling T, Joensuu H.. Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma. Clin Cancer Res 2011; 17 (14) 4806-4813
    Search in Google Scholar
  • Vandeven N, Lewis CW, Makarov V, Riaz N, Paulson KG, Hippe D. et al Merkel cell carcinoma patients presenting without a primary lesion have elevated markers of immunity, higher tumor mutation burden and improved survival. Clin Cancer Res 2017; 24 (04) 963-971
    Search in Google Scholar
  • Harms KL, Healy MA, Nghiem P, Sober AJ, Johnson TM, Bichakjian CK.. Analysis of prognostic factors from 9387 Merkel cell carcinoma cases forms the basis for the new 8th edition AJCC staging system. Ann Surg Oncol 2016; 23: 33643571
    Search in Google Scholar
  • Smiths VA, Camp ER, Lentsch EJ.. Merkel cell carcinoma: identification of prognostic factors unique to tumors located in the head and neck based on analysis of SEER data. Laryngoscope 2012; 122: 1283-1290
    Search in Google Scholar
  • Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Peñas PF. et al Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol 2008; 58 (03) 375-381
    Search in Google Scholar
  • Cheuk W, Kwan MY, Suster S, Chan JK.. Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch Pathol Lab Med 2001; 125 (02) 22831 <0228:IFTTFA>2.0.CO;2.
    Search in Google Scholar
  • Chen AM, Fu JM, Grekin RC, Margolis L.. Cancer of the Skin, Leibel and Phillips Textbook of Radiation Oncology. 3rd. 2010
    Search in Google Scholar
  • Andea AA, Coit DG, Amin B, Busam KJ.. Merkel cell carcinoma: histologic features and prognosis. Cancer 2008; 113 (09) 2549-2558
    Search in Google Scholar
  • Tello TL, Coggshall K, Yom SS, Yu SS.. Merkel cell carcinoma: an update review: current and future therapy. J Am Acad Dermatol 2018; 78 (03) 445-454
    Search in Google Scholar
  • Wong HH, Wang J.. Merkel cell carcinoma. Arch Pathol Lab Med 2010; 134 (11) 1711-1716
    Search in Google Scholar
  • Barksdale SK.. Advances in Merkel cell carcinoma from a pathologist's perspective. Pathology 2017; 49 (06) 568-574
    Search in Google Scholar
  • Martin B, Poblet E, Rios JJ, Kazakov D, Kutzner H, Brenn T. et al Merkel cell carcinoma with divergente differentiation: histopathological and immunohistochemical study of 15 cases with PCR analysis for Merkel cell polyomavirus. Histopathology 2013; 62 (05) 711
    Search in Google Scholar
  • Paulson KG, Lewis CW, Redman MW. et al Viral Oncoprotein antibodies as marker for recurrence of Merkel cell carcinoma: A prospective validation study. Cancer 2017; 123 (08) 1464-1474
    Search in Google Scholar
  • Treglia G, Annunziata S, Sobic-Saranovic D, Bertagna F, Caldarella C, Giovanella L.. The role of 18F-FDGPET and PET-CT in patients with sarcoidosis: an updated evidence-based review. Acad Radiol 2014; 21 (05) 675-684
    Search in Google Scholar
  • Amin M, Edge S, Greene F. et al AJCC Cancer Staging Manual. 8th. New York, NY: Springer; 2017
    Search in Google Scholar
  • Fields RC, Busam KJ, Chou JF, Panageas KS, Pulitzer MP, Kraus DH. et al Recurrence after complete surgical resection and selective use of adjuvant therapy for stage I through III Merkel cell carcinoma. Cancer 2012; 118 (13) 3311-3320
    Search in Google Scholar
  • Fields RC, Busam KJ, Chou JF, Panageas KS, Pulitzer MP, Kraus DH. et al Recurrence and survival in patients undergoing sentinel lymph node biopsy for Merkel cell carcinoma: analysis of 153 patients from a single institution. Ann Surg Oncol 2011; 18 (09) 252937
    Search in Google Scholar
  • Senchenkov A, Barnes SA, Moran SL.. Predictors of survival and recurrence in the surgical treatment of merkel cell carcinoma of the extremities. J Surg Oncol 2007; 95 (03) 229-234
    Search in Google Scholar
  • Bhatia S, Storer BE, Iyer JG, Moshiri A, Parvathaneni U, Byrd D. et al Adjuvant radiation therapy and chemotherapy in Merkel cell carcinoma: survival analyses of 6908 cases from the national cancer data base. J Natl Cancer Inst 2016; 108 (09) djw042
    Search in Google Scholar
  • Veness MJ, Perera L, McCourt J, Shannon J, Hughes TM, Morgan GJ. et al Merkel cell carcinoma: improved outcome with adjuvant radiotherapy. ANZ J Surg 2005; 75 (05) 275-281
    Search in Google Scholar
  • Poulsen M.. Merkel-cell carcinoma of the skin. Lancet Oncology 2004; 5 (10) 593-599
    Search in Google Scholar
  • Gillenwater AM, Hessel AC, Morrison WH. et al Merkel cell carcinoma of the Head and Neck Effect of Surgical Excision and Radiation on Recurrence and Survival. Arch Otolaryngol Head Neck Surg 2001; 127 (02) 149-154
    Search in Google Scholar
  • Hukko H, Bohling T, Koljonem V. et al Merkel cell carcinoma - a population- based epidemiological study in Finland with a clinical series of 181 cases. Eur J of Cancer 2012; 48: 737-742
    Search in Google Scholar
  • Lebbe C, Becker JC, Grob JJ. et al Diagnosis and treatment of Merkel Cell Carcinoma. European consensus-based interdisciplinary guideline. Eur J Cancer 2015; 51 (16) 2396-2403
    Search in Google Scholar
  • Miller SJ, Alam M, Andersen J, Berg D, Bichakjian CK, Bowen G. et al Merkel cell carcinoma: Clinical practice guidelines in oncology™. JNCCN Journal of the National Comprehensive Cancer Network 2006; 4 (07) 704-712
    Search in Google Scholar
  • Allen PJ, Zhang ZF, Coit DG.. Surgical management of Merkel cell carcinoma. Ann Surg 1999; 229 (01) 97-105
    Search in Google Scholar
  • 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; 23 (10) 929-933
    Search in Google Scholar
  • Lebbe C, Becker JC, Grob J-J, Malvehy J, del Marmol V, Pehamberger H. et al Diagnosis and treatment of Merkel cell carcinoma. European consensus-based interdisciplinary guideline. Eur J Cancer 2015; 51 (16) 2396-2403
    Search in Google Scholar
  • Medina-Franco H, Urist MM, Fiveash J, Heslin MJ, Bland KI, Beenken SW.. Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol 2001; 8 (03) 204-208
    Search in Google Scholar
  • Miller SJ, Alam M, Andersen J, Berg D, Bichakjian CK, Bowen G. et al Merkel cell carcinoma: Clinical practice guidelines in oncology™. JNCCN Journal of the National Comprehensive Cancer Network 2006; 4 (07) 704-712
    Search in Google Scholar
  • Schwartz JL, Griffith KA, Lowe L, Wong SL, McLean SA, Fullen DR. et al Features predicting sentinel lymph node positivity in Merkel cell carcinoma. J Clin Oncol 2011; 29 (08) 1036-1041
    Search in Google Scholar
  • Hitchcock CL, Bland KI, Laney RG, Franzini D, Harris B, Copeland EM.. Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment. Ann Surg 1988; 207 (02) 201-207
    Search in Google Scholar
  • Eng TY, Boersma MG, Fuller CD, Goytia V, Jones WE, Joyner M. et al A comprehensive review of the treatment of Merkel cell carcinoma. Am J Clin Oncol 2007; 30 (06) 624-636
    Search in Google Scholar
  • Gupta SG, Wang LC, Peñas PF, Gellenthin M, Lee SJ, Nghiem P.. Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: the Dana-Farber experience and meta-analysis of the literature. Arch Dermatol 2006; 142 (06) 685-690
    Search in Google Scholar
  • Sadeghi R, Adinehpoor Z, Maleki M, Fallahi B, Giovanella L, Treglia G.. Prognostic significance of sentinel lymph node mapping in Merkel cell carcinoma: systematic review and meta-analysis of prognostic studies. BioMed Res Int 2014; 2014
    Search in Google Scholar
  • Lewis KG, Weinstock MA, Weaver AL, Otley CC.. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol 2006; 142 (06) 693-700
    Search in Google Scholar
  • Poulsen M, Rischin D, Walpole E, Harvey J, Mackintosh J, Ainslie J. et al High- risk M e r k e l cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study-TROG 96:07. J Clin Oncol 2003; 21 (23) 4371-4376
    Search in Google Scholar
  • Poulsen MG, Rischin D, Porter I, Walpole E, Harvey J, Hamilton C. et al Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?. Int J Radiat Oncol Biol Phys 2006; 64 (01) 114-119
    Search in Google Scholar
  • Fields RC, Busam KJ, Chou JF. et al Recurrence after complete resection and selective use of adjuvant therapy for stage I through III Merkel Cell Carcinoma. Cancer 2012; 3311-3320
    Search in Google Scholar
  • 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; 141 (02) 137-141
    Search in Google Scholar
  • Adjuvant therapy of completely resected Merkel cell carcinoma with immune checkpoint blocking antibodies versus observation [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT02196961
  • NCCN Guidelines Version 1. 2018 Panel Members. . Merkel cell carcinoma 2018. 2018. p. https://www.nccn.org/professionals/physician_gls/P
  • Voog E, Biron P, Martin J-P, Blay J-Y.. Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer 1999; 85 (12) 2589-2595
    Search in Google Scholar
  • Tai PTH, Yu E, Winquist E, Hammond A, Stitt L, Tonita J. et al Chemotherapy in neuroendocrine/ Merkel cell carcinoma of the skin: case series and review of 204 Cases. J Clin Oncol 2000; 18: 2493-2499
    Search in Google Scholar
  • Becker JC, Lorenz E, Ugurel S, Eigentler TK, Kiecher F, Pföhler C. et al Evaluation of real-world treatment outcomes in patients with distant metastatic Merkel cell carcinoma following second-line chemotherapy in Europe. Oncotarget 2017; 8 (45) 79731-41
    Search in Google Scholar
  • Nghiem P, Kaufman HL, Bharmal M, Mahnke L, Phatak H, Becker JC.. Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma. Future Oncol 2017; 13 (14) 1263-1279
    Search in Google Scholar
  • Desch L, Kunstfeld R.. Merkel cell carcinoma: chemotherapy and emerging new therapeutic options. J Skin Cancer 2013; 2013: 327150
    Search in Google Scholar
  • Chan IS, Bhatia S, Lipson EJ. et al Immunotherapy for Merkel cell carcinoma: a turning point in patient care. Journal of Immunotherapy of Cancer 2018; 6: 23
    Search in Google Scholar
  • Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L. et al PD-1 blockade with pembrolizumab in advanced Merkel cell carcinoma. N Engl J Med 2016; 374 (26) 2542-2552
    Search in Google Scholar
  • Nghiem PT, Bhatia S, Lipson EJ. et al Durable Tumor Regression and Overall Survival in Patients with Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. Journal of Clinical Oncology 2019; 37 (09) 693-702
    Search in Google Scholar
  • Topalian SL, Bhatia S, Hollebecque A, Awada A, Boer JPD, Kudchadkar RR. et al Abstract CT074: non-comparative, open-label, multiple cohort, phase 1/2 study to evaluate nivolumab (NIVO) in patients with virus-associated tumors (CheckMate 358): efficacy and safety in Merkel cell carcinoma (MCC). Cancer Res 2017; 77: CT074CT074
    Search in Google Scholar
  • Topalian SL, Bhatia S, Kudchadkar RR. et al Nivolumab as neoadjuvant therapy in patients with resectable Merkel Cell Carcinoma in CheckMate 358. . 2018 ASCO Annual Meeting. Abstract 9505. Presented June 4 2018
    Search in Google Scholar
  • Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP. et al Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 2016; 17 (10) 1374-1385
    Search in Google Scholar
  • Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D'Angelo SP. et al Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after =1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer 2018; 6 (01) 1-7
    Search in Google Scholar
  • Joseph J, Zobniw C, Davis J, Anderson J, Trinh VA.. Avelumab: A review of Its application in metastatic Merkel cell carcinoma. Ann Pharmacother 2018; 1-8 https://doi.org/10.1177/1060028018768809
    Search in Google Scholar
  • D'Angelo SP, Russell J, Hassel JC, Lebbe C, Chmielowski B, Rabinowits G. et al First-line (1L) avelumab treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): preliminary data from an ongoing study. J Clin Oncol 2017; 35 (15_suppl): May 20 2017 9530-9530
    Search in Google Scholar
  • D'Angelo SP, Russell J, Lebbé C, Chmielowski B, Gambicher T, Grob J-J. et al Efficacy and safety of first-line avelumab treatment in patients with stage IV metastatic Merkel cell carcinoma. JAMA Oncol 2018; 10065: 1-5
    Search in Google Scholar
  • Georges S, Shah PK, Shapiro I. et al Integrative molecular analysis of metastatic Merkel cell carcinoma to identify predictive biomarkers of response to avelumab. 2019 ASCO Annual Meeting. Abstract 9569
  • Chan IS, Bhatia S, Kaufman HL, Lipson EJ.. Immunotherapy for Merkel cell carcinoma: a turning point in patient care. J Immunother Cancer 2018; 6: 23
    Search in Google Scholar
  • Wang M, Ma X, Guo L, Xia F.. Safety and efficacy profile of pembrolizumab in solid cancer: pooled reanalysis based on randomized controlled trials. Drug Des Devel Ther 2017; 11: 2851-2860
    Search in Google Scholar
  • Kelly K, Infante JR, Taylor MH, Patel MR, Wong DJ, Iannotti N. et al Safety profile of avelumab in patients with advanced solid tumors: a pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Cancer 2018; 124 (09) 2010-2017
    Search in Google Scholar
  • www.clinicaltrials.gov/ct2/show/NCT01758458 Consulted in April 22 2018
  • www.clinicaltrials.gov/ct2/show/NCT03071406 Consulted in April 22 2018
  • www.clinicaltrials.gov/ct2/show/NCT02196961 Consulted in April 22 2018
  • www.clinicaltrials.gov/ct2/show/NCT03271372 Consulted in April 22 2018