Uveal melanoma

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 Ryan Nguyen, DO
University of Illinois at Chicago
Chicago, IL, USA
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 Elizabeth Buchbinder, MD
Dana-Farber Cancer Institute
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Note: this page is for regimens specific to uveal melanoma; see the main melanoma page for other regimens.

13 regimens on this page
13 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

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.

Chemotherapy

21-day cycles

References

  1. 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 contains dosing details in manuscript PubMed NCT01974752
  2. 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 contains dosing details in manuscript 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

Immunotherapy

21-day cycle for up to 4 cycles

References

  1. 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 contains dosing details in manuscript 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

  1. 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 contains dosing details in manuscript 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)

Note: in the control group, "all available treatments including surgery and other experimental treatments were accepted".

Chemotherapy

References

  1. 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
  2. FOCUSHCC: 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

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

Immunotherapy

21-day cycles

References

  1. 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 contains dosing details in manuscript 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

  1. 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 contains dosing details in manuscript PubMed NCT03070392
    1. 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 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

Chemotherapy

21-day cycles

References

  1. 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 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

  1. 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 contains dosing details in abstract 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

21-day cycle for 4 cycles, then 28-day cycle for up to 23 cycles (2 years total)

References

  1. 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 contains dosing details in manuscript 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

Local therapy

1 or more treatments

References

  1. 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

Targeted therapy

Continued indefinitely

References

  1. 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 contains dosing details in manuscript 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

Chemotherapy

28-day cycles

References

  1. 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 contains dosing details in abstract 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

References

  1. 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
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