Difference between revisions of "Merkel cell carcinoma"
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Warner-admin (talk | contribs) m (Text replacement - "(NCT[0-9]{8})" to "[https://clinicaltrials.gov/ct2/show/$1 Clinical Trial Registry]") |
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===References=== | ===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. [https://doi.org/10.1056/NEJMoa1603702 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927341/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27093365/ PubMed] NCT02267603 | + | # '''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. [https://doi.org/10.1056/NEJMoa1603702 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927341/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27093365/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT02267603 Clinical Trial Registry] |
##'''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. [https://doi.org/10.1200/jco.18.01896 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6424137/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30726175/ PubMed] | ##'''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. [https://doi.org/10.1200/jco.18.01896 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6424137/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30726175/ PubMed] | ||
##'''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. [https://doi.org/10.1136/jitc-2021-002478 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8061836/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33879601/ PubMed] | ##'''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. [https://doi.org/10.1136/jitc-2021-002478 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8061836/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33879601/ PubMed] | ||
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!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
| − | |[https://clinicaltrials.gov/ct2/show/NCT03599713 Awaiting publication (PODIUM-201)] | + | |[https://clinicaltrials.gov/ct2/show/[https://clinicaltrials.gov/ct2/show/NCT03599713 Clinical Trial Registry] Awaiting publication (PODIUM-201)] |
|2019-2022 | |2019-2022 | ||
| style="background-color:#91cf61" |Phase 2 (RT) | | style="background-color:#91cf61" |Phase 2 (RT) | ||
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</div></div> | </div></div> | ||
===References=== | ===References=== | ||
| − | #'''PODIUM-201:''' NCT03599713 | + | #'''PODIUM-201:''' [https://clinicaltrials.gov/ct2/show/NCT03599713 Clinical Trial Registry] |
=Metastatic or advanced disease, subsequent lines of therapy= | =Metastatic or advanced disease, subsequent lines of therapy= | ||
| Line 114: | Line 114: | ||
===References=== | ===References=== | ||
<!-- # '''Abstract:''' Howard Kaufman, Jeffery Scott Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P. D'Angelo, Kent C. Shih, Celeste Lebbe, Gerald P Linette, Michele Milella, Isaac Brownell, Karl D. Lewis, Jochen H. Lorch, Kevin M. Chin, Lisa Mahnke, Anja von Heydebreck, Jean-Marie Cuillerot, Paul Nghiem. Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic Merkel cell carcinoma previously treated with chemotherapy: Results of the phase 2 JAVELIN Merkel 200 trial. 2016 ASCO Annual Meeting abstract 9508. [http://meetinglibrary.asco.org/content/168263-176 link to abstract] --> | <!-- # '''Abstract:''' Howard Kaufman, Jeffery Scott Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P. D'Angelo, Kent C. Shih, Celeste Lebbe, Gerald P Linette, Michele Milella, Isaac Brownell, Karl D. Lewis, Jochen H. Lorch, Kevin M. Chin, Lisa Mahnke, Anja von Heydebreck, Jean-Marie Cuillerot, Paul Nghiem. Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic Merkel cell carcinoma previously treated with chemotherapy: Results of the phase 2 JAVELIN Merkel 200 trial. 2016 ASCO Annual Meeting abstract 9508. [http://meetinglibrary.asco.org/content/168263-176 link to abstract] --> | ||
| − | # '''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. [https://doi.org/10.1016/s1470-2045(16)30364-3 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587154/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27592805/ PubMed] content property of [http://hemonc.org HemOnc.org] NCT02155647 | + | # '''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. [https://doi.org/10.1016/s1470-2045(16)30364-3 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587154/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27592805/ PubMed] content property of [http://hemonc.org HemOnc.org] [https://clinicaltrials.gov/ct2/show/NCT02155647 Clinical Trial Registry] |
## '''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. [https://jitc.biomedcentral.com/articles/10.1186/s40425-017-0310-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774167/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29347993/ PubMed] | ## '''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. [https://jitc.biomedcentral.com/articles/10.1186/s40425-017-0310-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774167/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29347993/ PubMed] | ||
## '''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. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2675910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885245/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29566106/ PubMed] | ## '''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. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2675910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885245/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29566106/ PubMed] | ||
Revision as of 15:04, 31 May 2023
| Section editor | |
|---|---|
 |
Elizabeth Buchbinder, MD Dana-Farber Cancer Institute Boston, MA |
3 regimens on this page
3 variants on this page
|
Guidelines
Alberta Health Services
- 2019: Merkel Cell Carcinoma
NCCN
Older
- 2014: Bichakjian et al. Merkel cell carcinoma, version 1.2014 PubMed
SITC
- 2022: Silk et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer
Metastatic or advanced disease, first-line therapy
Pembrolizumab monotherapy
Regimen
| 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
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 contains dosing details in manuscript PubMed Clinical Trial Registry
- 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 PubMed
- 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 PubMed
Retifanlimab monotherapy
Regimen
| Study | Dates of enrollment | Evidence |
|---|---|---|
| [https://clinicaltrials.gov/ct2/show/NCT03599713 Clinical Trial Registry Awaiting publication (PODIUM-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
- PODIUM-201: Clinical Trial Registry
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, 30 to 60 minutes prior to Avelumab (Bavencio)
- Paracetamol/acetaminophen (dose not given) once on day 1, 30 to 60 minutes prior to Avelumab (Bavencio)
- 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. link to original article contains dosing details in manuscript link to PMC article PubMed content property of HemOnc.org Clinical Trial Registry
- 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 PubMed
- 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 PubMed
- 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 PubMed
- 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 PubMed