Merkel cell carcinoma

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For placebo or observational studies in this condition, please visit this page. 
Last updated on 2024-12-02:3 regimens on this page
5 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==Alberta Health Services==
*2019: Merkel Cell Carcinoma EuroPMC
==ESMO/EURACAN==
* 2024: Lugowska et al. Merkel-cell carcinoma: ESMO–EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up. EuroPMC
==NCCN==
*NCCN Guidelines - Merkel Cell Carcinoma
**2024: Schmults et al. NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024 EuroPMC
**2018: Bichakjian et al. Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. link to PMC article EuroPMC
**2014: Bichakjian et al. Merkel cell carcinoma, version 1.2014. link to PMC article EuroPMC
**2009: Miller et al. Merkel cell carcinoma. link to PMC article EuroPMC
**2006: Miller et al. Merkel cell carcinoma. EuroPMC
**2004: No authors listed. Merkel cell carcinoma. Clinical practice guidelines in oncology. EuroPMC
==SITC==
*2022: Silk et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer link to PMC article EuroPMC
=Metastatic or advanced disease, first-line therapy=
==Pembrolizumab monotherapy==
===Regimen variant #1, flat dosing===
Study 	Dates of enrollment 	Evidence 	Efficacy
Mortier et al. 2024 (KEYNOTE-913)	2019-02-25 to 2020-11-17	Non-randomized Phase 3 (RT)	ORR: 49% (95% CI 35-63%)
====Immunotherapy====
*Pembrolizumab (Keytruda) 2 mg/kg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===Regimen variant #2, weight-based===
Study 	Dates of enrollment	Evidence 	Efficacy
Nghiem et al. 2016 (KEYNOTE-017)	2015-01 to 2015-12 	Phase 2 (RT)	ORR: 58% (95% CI 43-72%)1
1Reported efficacy is based on the 2021 update.
====Immunotherapy====
*Pembrolizumab (Keytruda) 2 mg/kg IV once on day 1
21-day cycle for up to 35 cycles (2 years) or until CR
===Regimen variant #3, weight-based with cap (pediatric dosing)===
Study 	Dates of enrollment 	Evidence 	Efficacy
Mortier et al. 2024 (KEYNOTE-913)	2019-02-25 to 2020-11-17	Non-randomized Phase 3 (RT)	ORR: 49% (95% CI 35-63%)
====Immunotherapy====
*Pembrolizumab (Keytruda) 2 mg/kg (maximum dose of 200 mg) IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===References===
# KEYNOTE-017: Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016 Jun 30;374(26):2542-52. Epub 2016 Apr 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02267603
##Update: Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019 Mar 20;37(9):693-702. Epub 2019 Feb 6. link to original article link to PMC article EuroPMC
##Update: Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker A, Burgess MA, Hanks BA, Olencki T, Kendra K, Church C, Akaike T, Ramchurren N, Shinohara MM, Salim B, Taube JM, Jensen E, Kalabis M, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. J Immunother Cancer. 2021 Apr;9(4):e002478. link to original article link to PMC article EuroPMC
#KEYNOTE-913: Mortier L, Villabona L, Lawrence B, Arance A, Butler MO, Beylot-Barry M, Saiag P, Samimi M, Ascierto PA, Spada F, De Pontville M, Maio M, Berrocal A, Espinosa E, Capdevila J, Levin M, Das D, Krepler C, Grebennik D, Chiarion-Sileni V. Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study. Am J Clin Dermatol. 2024 Nov;25(6):987-996. Epub 2024 Oct 8. link to original article link to PMC article EuroPMC NCT03783078
==Retifanlimab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Awaiting publication (POD1UM-201)	2019-2022 	Phase 2 (RT)
====Immunotherapy====
*Retifanlimab (Zynyz) 500 mg IV over 30 minutes once on day 1
28-day cycle for up to 24 cycles (2 years)
===References===
#POD1UM-201: NCT03599713
=Metastatic or advanced disease, subsequent lines of therapy=
==Avelumab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Efficacy
Kaufman et al. 2016 (JAVELIN Merkel 200)	2014-07-25 to 2015-09-03	Phase 2 (RT)	33% (95% CI: 23–44)1
1Reported efficacy is based on the 2020 update.
====Prior treatment criteria====
*Failure of at least one previous line of chemotherapy for metastatic disease.
====Immunotherapy====
*Avelumab (Bavencio) 10 mg/kg IV over 60 minutes once on day 1
====Supportive therapy====
*H1-antihistamine, such as diphenhydramine (dose & route not given) once on day 1, given 30 to 60 minutes prior to avelumab
*Paracetamol/acetaminophen (dose not given) once on day 1, given 30 to 60 minutes prior to avelumab
*The Bavencio package insert suggests "Premedicate with acetaminophen and an antihistamine for the first 4 infusions and subsequently as needed."
14-day cycles
===References===
# JAVELIN Merkel 200: Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot JM, Nghiem P. 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. Epub 2016 Sep 1. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC content property of HemOnc.org NCT02155647
## Update: Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Milella M, Brownell I, Lewis KD, Lorch JH, von Heydebreck A, Hennessy M, Nghiem P. 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 Jan 19;6(1):7. link to original article link to PMC article EuroPMC
## Update: D'Angelo SP, Russell J, Lebbé C, Chmielowski B, Gambichler T, Grob JJ, Kiecker F, Rabinowits G, Terheyden P, Zwiener I, Bajars M, Hennessy M, Kaufman HL. Efficacy and safety of first-line avelumab treatment in patients with stage IV metastatic Merkel cell carcinoma: a preplanned interim analysis of a clinical trial. JAMA Oncol. 2018 Sep 1;4(9):e180077. Epub 2018 Sep 13. link to original article link to PMC article EuroPMC
##Update: D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Georges S, Shah P, Ellers-Lenz B, Bajars M, Güzel G, Nghiem PT. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer. 2020 May;8(1):e000674. link to original article link to PMC article EuroPMC
##Update: D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Xiong H, Guezel G, Nghiem PT. Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up. ESMO Open. 2021 Dec;6(6):100290. Epub 2021 Oct 26. link to original article link to PMC article EuroPMC
Category:Merkel cell carcinoma regimens
Category:Disease-specific pages
Category:Non-melanoma skin cancers