Uveal melanoma

Back to Top
Note: this page is for regimens specific to uveal melanoma; see the main melanoma page for other regimens.
Last updated on 2024-07-23:13 regimens on this page
14 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.
==NCCN==
*NCCN Guidelines - Melanoma: Uveal
=Metastatic or unresectable disease, untreated=
==Dacarbazine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Carvajal et al. 2018 (SUMIT) 	2014-04 to 2015-02 	Phase 3 (C)	Dacarbazine & Selumetinib	Did not meet primary endpoint of PFSMedian PFS: 1.8 vs 2.8 mo(HR 1.28, 95% CI 0.79-2.08)
Nathan et al. 2021 (IMCgp100-202)	2017-2020 	Phase 3 (C)	Tebentafusp 	Shorter OS1Median OS: 16.9 vs 21.6 mo(HR 1.47, 95% CI 1.15-1.85)
1Reported efficacy for IMCgp100-202 is based on the 2023 update.
Note: prior nonsystemic therapy was allowed in SUMIT.
====Chemotherapy====
*Dacarbazine (DTIC) 1000 mg/m2 IV once on day 1
21-day cycles
===References===
# SUMIT: Carvajal RD, Piperno-Neumann S, Kapiteijn E, Chapman PB, Frank S, Joshua AM, Piulats JM, Wolter P, Cocquyt V, Chmielowski B, Evans TRJ, Gastaud L, Linette G, Berking C, Schachter J, Rodrigues MJ, Shoushtari AN, Clemett D, Ghiorghiu D, Mariani G, Spratt S, Lovick S, Barker P, Kilgour E, Lai Z, Schwartz GK, Nathan P. Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicenter, randomized trial (SUMIT). J Clin Oncol. 2018 Apr 20;36(12):1232-1239. Epub 2018 Mar 12. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01974752
# IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03070392
==Ipilimumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020 	Phase 3 (C)	Tebentafusp	Shorter OS1Median OS: 16.9 vs 21.6 mo(HR 1.47, 95% CI 1.15-1.85)
1Reported efficacy is based on the 2023 update.
====Immunotherapy====
*Ipilimumab (Yervoy) 3 mg/kg IV once on day 1
21-day cycle for up to 4 cycles
===References===
# IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03070392
==Ipilimumab & Nivolumab==
===Regimen===
Study 	Dates of enrollment	Evidence
Piulats et al. 2021 (GEM-1402)	2016-04 to 2017-06 	Phase 2
====Immunotherapy====
*Ipilimumab (Yervoy) as follows:
**Cycles 1 to 4: 3 mg/kg IV over 90 minutes once on day 1
*Nivolumab (Opdivo) as follows:
**Cycles 1 to 4: 1 mg/kg IV over 60 minutes once on day 1
**Cycle 5 onwards: 3 mg/kg IV over 60 minutes once on day 1
21-day cycle for 4 cycles, then 14-day cycles
===References===
# GEM-1402: Piulats JM, Espinosa E, de la Cruz Merino L, Varela M, Alonso Carrión L, Martín-Algarra S, López Castro R, Curiel T, Rodríguez-Abreu D, Redrado M, Gomà M, Rullán AJ, Calvo González A, Berrocal-Jaime A. Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol. 2021 Feb 20;39(6):586-598. Epub 2021 Jan 8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02626962
==Melphalan isolated hepatic perfusion==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Olofsson Bagge et al. 2023 (SCANDIUM)	2013-07 to 2021-03 	Phase 3 (C) 	Investigator's choice of therapy	Longer PFS (secondary endpoint)Median PFS: 7.4 vs 3.3 mo(HR 0.21, 95% CI 0.12-0.36)
Zager et al. 2024 (FOCUSHCC) 	2016-02 to 2020-10 	Non-randomized phase 3 (RT)	 	
Note: in the control group of SCANDIUM, "all available treatments including surgery and other experimental treatments were accepted".
====Chemotherapy====
*Melphalan for Injection-Hepatic Delivery System (Hepzato Kit) 3 mg/kg IA once on day 1
**Dosing is based on ideal body weight
6- to 8-week cycle for up to 6 cycles
===References===
#SCANDIUM: Olofsson Bagge R, Nelson A, Shafazand A, All-Eriksson C, Cahlin C, Elander N, Helgadottir H, Kiilgaard JF, Kinhult S, Ljuslinder I, Mattsson J, Rizell M, Sternby Eilard M, Ullenhag GJ, Nilsson JA, Ny L, Lindnér P. Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial). J Clin Oncol. 2023 Jun 1;41(16):3042-3050. Epub 2023 Mar 20. link to original article link to PMC article EuroPMC NCT01785316
#FOCUSHCC: Zager JS, Orloff M, Ferrucci PF, Choi J, Eschelman DJ, Glazer ES, Ejaz A, Howard JH, Richtig E, Ochsenreither S, Reddy SA, Lowe MC, Beasley GM, Gesierich A, Bender A, Gschnell M, Dummer R, Rivoire M, Arance A, Fenwick SW, Sacco JJ, Haferkamp S, Weishaupt C, John J, Wheater M, Ottensmeier CH. Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study. Ann Surg Oncol. 2024 Aug;31(8):5340-5351. Epub 2024 May 4. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT02678572
==Pembrolizumab monotherapy==
===Regimen variant #1, weight-based===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020 	Phase 3 (C)	Tebentafusp	Shorter OS1Median OS: 16.9 vs 21.6 mo(HR 1.47, 95% CI 1.15-1.85)
1Reported efficacy is based on the 2023 update.
====Immunotherapy====
*Pembrolizumab (Keytruda) 2 mg/kg (maximum dose of 200 mg) IV once on day 1
21-day cycles
===Regimen variant #2, flat dosing===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020 	Phase 3 (C)	Tebentafusp	Shorter OS1Median OS: 16.9 vs 21.6 mo(HR 1.47, 95% CI 1.15-1.85)
1Reported efficacy is based on the 2023 update.
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycles
===References===
# IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03070392
==Tebentafusp monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Nathan et al. 2021 (IMCgp100-202)	2017-2020 	Phase 3 (E-RT-switch-ooc)	Investigator's choice of:1a. Dacarbazine1b. Ipilimumab1c. Pembrolizumab	Longer OS1 (primary endpoint)Median OS: 21.6 vs 16.9 mo(HR 0.68, 95% CI 0.54-0.87)
1Reported efficacy is based on the 2023 update.
====Immunotherapy====
*Tebentafusp (Kimmtrak) as follows:
**Cycle 1: 20 mcg IV once on day 1
**Cycle 2: 30 mcg IV once on day 1
**Cycle 3 onwards: 68 mcg IV once on day 1
7-day cycles
===References===
# IMCgp100-202: Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03070392
##Update: Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain JF, Schlaak M, Butler MO, Sullivan RJ, Dummer R, Kirkwood JM, Orloff M, Sacco JJ, Ochsenreither S, Joshua AM, Gastaud L, Curti B, Piulats JM, Salama AKS, Shoushtari AN, Demidov L, Milhem M, Chmielowski B, Kim KB, Carvajal RD, Hamid O, Collins L, Ranade K, Holland C, Pfeiffer C, Nathan P. Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2023 Dec 14;389(24):2256-2266. Epub 2023 Oct 21. link to original article link to PMC article EuroPMC
=Metastatic or unresectable disease, all lines of therapy=
==Dacarbazine monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Carvajal et al. 2014 (MSK 10-053)	2010-08-25 to 2013-07-23	Randomized Phase 2 (C)	Selumetinib	Shorter PFSMedian PFS: 7 vs 15.9 weeks(HR 2.17, 95% CI 1.41-3.33)
====Prior treatment criteria====
*MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
====Chemotherapy====
*Dacarbazine (DTIC) 1000 mg/m2 IV once on day 1
21-day cycles
===References===
# MSK 10-053: Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01143402
==Fotemustine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Leyvraz et al. 2014 (EORTC 18021)	2005-2011 	Phase 3 (C)	Fotemustine; HAI	Did not meet primary endpoint of OSMedian OS: 13.8 vs 14.6 mo(HR 0.92, 95% CI 0.67-1.27)
====Chemotherapy====
*Fotemustine (Muphoran) as follows:
**Cycle 1: 100 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
**Cycle 2 onwards: 100 mg/m2 IV once on day 1
8-week course, then 21-day cycles
===References===
# EORTC 18021: Leyvraz S, Piperno-Neumann S, Suciu S, Baurain JF, Zdzienicki M, Testori A, Marshall E, Scheulen M, Jouary T, Negrier S, Vermorken JB, Kaempgen E, Durando X, Schadendorf D, Karra Gurunath R, Keilholz U. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol. 2014 Mar;25(3):742-6. Epub 2014 Feb 7. link to original article link to PMC article dosing details in supplement have been reviewed by our editors EuroPMC NCT00110123
==Ipilimumab & Nivolumab==
===Regimen===
Study 	Dates of enrollment 	Evidence
Pelster et al. 2020 (MDACC 2011-0919)	2015-07-07 to 2018-03-07	Phase 2
====Immunotherapy====
*Ipilimumab (Yervoy) as follows:
**Cycles 1 to 4: 3 mg/kg IV once on day 1
*Nivolumab (Opdivo) as follows:
**Cycles 1 to 4: 1 mg/kg IV once on day 1
**Cycle 5 onwards: 480 mg IV once on day 1
21-day cycle for 4 cycles, then 28-day cycle for up to 23 cycles (2 years total)
===References===
# MDACC 2011-0919: Pelster MS, Gruschkus SK, Bassett R, Gombos DS, Shephard M, Posada L, Glover MS, Simien R, Diab A, Hwu P, Carter BW, Patel SP. Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study. J Clin Oncol. 2021 Feb 20;39(6):599-607. Epub 2020 Oct 30. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01585194
==TACE monotherapy==
TACE: Trans-Arterial Chemo-Embolization
===Regimen===
Study 	Dates of enrollment	Evidence
Mavligit et al. 1988	1983-11 to 1987-04 	Non-randomized
====Local therapy====
*TACE 
1 or more treatments
===References===
# Mavligit GM, Charnsangavej C, Carrasco CH, Patt YZ, Benjamin RS, Wallace S. Regression of ocular melanoma metastatic to the liver after hepatic arterial chemoembolization with cisplatin and polyvinyl sponge. JAMA. 1988 Aug 19;260(7):974-6. link to original article EuroPMC
==Selumetinib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Carvajal et al. 2014 (MSK 10-053)	2010-08-25 to 2013-07-23	Randomized Phase 2 (E-switch-ooc)	1a. Dacarbazine1b. Temozolomide	Longer PFS (primary endpoint)Median PFS: 15.9 vs 7 wk(HR 0.46, 95% CI 0.30-0.71)
====Prior treatment criteria====
*MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
====Targeted therapy====
*Selumetinib (Koselugo) 75 mg PO twice per day
Continued indefinitely
===References===
# MSK 10-053: Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01143402
==Temozolomide monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Carvajal et al. 2014 (MSK 10-053)	2010-08-25 to 2013-07-23	Randomized Phase 2 (C)	Selumetinib	Shorter PFSMedian PFS: 7 vs 15.9 weeks(HR 2.17, 95% CI 1.41-3.33)
====Prior treatment criteria====
*MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
====Chemotherapy====
*Temozolomide (Temodar) 150 mg/m2 PO once per day on days 1 to 5
28-day cycles
===References===
# MSK 10-053: Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01143402
==TILs==
TILs: Tumor Ifiltrating Lymphocytes
===Regimen===
Study 	Dates of enrollment 	Evidence
Chandran et al. 2017 (NCI 13-C-0093)	2013-06-07 to 2016-07-14	Phase 2
====Preceding treatment====
*FC lymphodepletion
====Immunotherapy====
*Autologous TILs
===References===
# NCI 13-C-0093: Chandran SS, Somerville RPT, Yang JC, Sherry RM, Klebanoff CA, Goff SL, Wunderlich JR, Danforth DN, Zlott D, Paria BC, Sabesan AC, Srivastava AK, Xi L, Pham TH, Raffeld M, White DE, Toomey MA, Rosenberg SA, Kammula US. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study. Lancet Oncol. 2017 Jun;18(6):792-802. Epub 2017 Apr 7. link to original article link to PMC article EuroPMC NCT01814046
Category:Uveal melanoma regimens
Category:Disease-specific pages
Category:Skin cancers