Uveal melanoma
Page editor | Section editor | ||
---|---|---|---|
Ryan Nguyen, DO University of Illinois at Chicago Chicago, IL, USA |
Elizabeth Buchbinder, MD Dana-Farber Cancer Institute Boston, MA, USA |
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.
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 PFS |
Nathan et al. 2021 (IMCgp100-202) | 2017-2020 | Phase 3 (C) | Tebentafusp | Inferior OS |
Note: prior nonsystemic therapy was allowed in SUMIT.
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 PubMed 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 PubMed NCT03070392
Ipilimumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Nathan et al. 2021 (IMCgp100-202) | 2017-2020 | Phase 3 (C) | Tebentafusp | Inferior OS |
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 PubMed 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 PubMed 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 | Superior 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 PubMed 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 PubMed 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 | Inferior OS |
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 | Inferior OS |
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 PubMed 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. Dacarbazine 1b. Ipilimumab 1c. Pembrolizumab |
Superior 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 PubMed 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 PubMed
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 | Inferior PFS |
Prior treatment criteria
- MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
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 PubMed 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 OS |
Chemotherapy
- Fotemustine (Muphoran) as follows:
- Cycle 1: 100 mg/m2 IV 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 abstract have been reviewed by our editors PubMed 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 PubMed 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 |
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 PubMed
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. Dacarbazine 1b. Temozolomide |
Superior 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
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 PubMed 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 | Inferior PFS |
Prior treatment criteria
- MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
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 PubMed 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 PubMed NCT01814046