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Page editor		Section editor
	Ryan Nguyen, DO University of Illinois at Chicago Chicago, IL, USA LinkedIn		Elizabeth Buchbinder, MD Dana-Farber Cancer Institute Boston, MA, USA LinkedIn

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

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 PFS
Nathan et al. 2021 (IMCgp100-202)	2017-2020	Phase 3 (C)	Tebentafusp	Inferior OS

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 contains dosing details in manuscript 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 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

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 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

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

Melphalan for Injection-Hepatic Delivery System (Hepzato Kit)

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
FOCUS_HCC: 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

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 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

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

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 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 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

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 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

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 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

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 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

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 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

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

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-{{#lst:Section editor transclusions|mel}}
+<span id="BackToTop"></span>
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
+[[#top|Back to Top]]
+</div>
+{{#lst:Editorial board transclusions|mel}}
 <big>'''Note: this page is for regimens specific to uveal melanoma; see the [[Melanoma|main melanoma page]] for other regimens.</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
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 {{TOC limit|limit=3}}
 =Guidelines=
-==[https://www.nccn.org/ NCCN]==
+'''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.'''
-*[https://www.nccn.org/professionals/physician_gls/pdf/uveal.pdf NCCN Guidelines - Uveal Melanoma]
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1488 NCCN Guidelines - Melanoma: Uveal]
-=Metastatic or unresectable disease=
-==Dacarbazine monotherapy {{#subobject:d3599b|Regimen=1}}==
-===Regimen {{#subobject:bede4c|Variant=1}}===
+=Metastatic or unresectable disease, untreated=
+==Dacarbazine monotherapy {{#subobject:jg399b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:bensyc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ Carvajal et al. 2014 (MSK 10-053)]
-|2010-2013
-|style="background-color:#1a9851"|Randomized Phase 2 (C)
-|[[#Selumetinib_monotherapy|Selumetinib]]
-| style="background-color:#fee08b" |Might have inferior OS
 |-
 |[https://doi.org/10.1200/JCO.2017.74.1090 Carvajal et al. 2018 (SUMIT)]
-|2014-2015
+|2014-04 to 2015-02
 |style="background-color:#1a9851"|Phase 3 (C)
-|[[#Dacarbazine_.26_Selumetinib_99|Dacarbazine & Selumetinib]]
+|[[#Dacarbazine_.26_Selumetinib_999|Dacarbazine & Selumetinib]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
@@ Line 43: / Line 40: @@
 |-
 |}
+''Note: prior nonsystemic therapy was allowed in SUMIT.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycles'''
+</div></div>
-===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. [https://jamanetwork.com/journals/jama/fullarticle/1881312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24938562 PubMed] NCT01143402
-# '''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. [https://doi.org/10.1200/JCO.2017.74.1090 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29528792 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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] NCT03070392
-==Fotemustine monotherapy {{#subobject:92d0c6|Regimen=1}}==
-===Regimen {{#subobject:ff4f50|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433517/ Leyvraz et al. 2014 (EORTC 18021)]
-|2005-2011
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Fotemustine_monotherapy|Fotemustine]]; HAI
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|}
-====Chemotherapy====
-*[[Fotemustine (Muphoran)]] as follows:
-**Weeks 1 to 3: 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-**Weeks 4 to 8: no treatment
-**Week 9 onwards: 100 mg/m<sup>2</sup> IV once on day 1, every 3 weeks
-'''8-week induction cycle, 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. [https://doi.org/10.1093/annonc/mdt585 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433517/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24510314 PubMed] NCT00110123
+# '''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. [https://doi.org/10.1200/JCO.2017.74.1090 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29528792/ PubMed] [https://clinicaltrials.gov/study/NCT01974752 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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] [https://clinicaltrials.gov/study/NCT03070392 NCT03070392]
 ==Ipilimumab monotherapy {{#subobject:dga21b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:ance4c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 98: / Line 66: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Ipilimumab (Yervoy)]] 3 mg/kg IV once on day 1
 '''21-day cycle for up to 4 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] NCT03070392
+# '''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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] [https://clinicaltrials.gov/study/NCT03070392 NCT03070392]
+==Ipilimumab & Nivolumab {{#subobject:5jiw10|Regimen=1}}==
-==Ipilimumab & Nivolumab {{#subobject:51gu10|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:3a481c|Variant=1}}===
-===Regimen variant #1, "NIVO1+IPI3", flat-dose maintenance {{#subobject:3a481c|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 33%"|Study
-!style="width: 25%"|Study
+!style="width: 33%"|Dates of enrollment
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://ascopubs.org/doi/10.1200/JCO.20.00550 Piulats et al. 2021 (GEM-1402)]
+|[https://doi.org/10.1200/JCO.20.00550 Piulats et al. 2021 (GEM-1402)]
+|2016-04 to 2017-06
 | style="background-color:#91cf61" |Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Ipilimumab (Yervoy)]] as follows:
-**Cycles 1 to 4: 3 mg/kg IV once on day 1
+**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 once on day 1
+**Cycles 1 to 4: 1 mg/kg IV over 60 minutes once on day 1
-**Cycle 5 onwards: 3 mg/kg IV 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'''
+</div></div>
+===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. [https://doi.org/10.1200/JCO.20.00550 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33417511/ PubMed] [https://clinicaltrials.gov/study/NCT02626962 NCT02626962]
-===Regimen variant #2, "NIVO3+IPI1", flat-dose maintenance {{#subobject:3a48jc|Variant=1}}===
+==Melphalan isolated hepatic perfusion {{#subobject:i4bhwb|Regimen=1}}==
-{| class="wikitable" style="width: 40%; text-align:center;"
+<div class="toccolours" style="background-color:#eeeeee">
-!style="width: 25%"|Study
+===Regimen {{#subobject:54vx2v|Variant=1}}===
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://ascopubs.org/doi/10.1200/JCO.20.00605 Pelster et al. 2020 (MDACC 2011-0919)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10414734/ Olofsson Bagge et al. 2023 (SCANDIUM)]
-| style="background-color:#91cf61" |Phase 2
+|2013-07 to 2021-03
+|style="background-color:#1a9851"|Phase 3 (C)
+|Investigator's choice of therapy
+| style="background-color:#1a9850" |Superior PFS (secondary endpoint)<br>Median PFS: 7.4 vs 3.3 mo<br>(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".''
-====Immunotherapy====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
-*[[Ipilimumab (Yervoy)]] as follows:
+*[[Melphalan for Injection-Hepatic Delivery System (Hepzato Kit)]]
-**Cycles 1 to 4: 1 mg/kg IV once on day 1
+</div></div>
-*[[Nivolumab (Opdivo)]] as follows:
-**Cycles 1 to 4: 3 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 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. [https://ascopubs.org/doi/10.1200/JCO.20.00550 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33417511/ PubMed] NCT02626962
+#'''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. [https://doi.org/10.1200/jco.22.01705 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10414734/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36940407/ PubMed] [https://clinicaltrials.gov/study/NCT01785316 NCT01785316]
-# '''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. [https://ascopubs.org/doi/10.1200/JCO.20.00605 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33125309/ PubMed] NCT01585194
+#'''FOCUS<sub>HCC</sub>:''' [https://clinicaltrials.gov/study/NCT02678572 NCT02678572]
 ==Pembrolizumab monotherapy {{#subobject:dhuahb|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, weight-based {{#subobject:bed6av|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 169: / Line 141: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Pembrolizumab (Keytruda)]] 2 mg/kg (maximum dose of 200 mg) IV once on day 1
 '''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, flat dosing {{#subobject:b7d6av|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 189: / Line 162: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycles'''
+</div></div>
+===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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] [https://clinicaltrials.gov/study/NCT03070392 NCT03070392]
+==Tebentafusp monotherapy {{#subobject:4ugh17|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:6eug88|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/nejmoa2103485 Nathan et al. 2021 (IMCgp100-202)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-316-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2017-2020
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
+|Investigator's choice of:<br>1a. [[#Dacarbazine_monotherapy|Dacarbazine]]<br>1b. [[#Ipilimumab_monotherapy|Ipilimumab]]<br>1c. [[#Pembrolizumab_monotherapy|Pembrolizumab]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 21.6 vs 16.9 mo<br>(HR 0.68, 95% CI 0.54-0.87)
+|-
+|}
+''<sup>1</sup>Reported efficacy is based on the 2023 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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'''
+</div></div>
+===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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] [https://clinicaltrials.gov/study/NCT03070392 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. [https://doi.org/10.1056/nejmoa2304753 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37870955/ PubMed]
+=Metastatic or unresectable disease, all lines of therapy=
+==Dacarbazine monotherapy {{#subobject:d3599b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:bede4c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ Carvajal et al. 2014 (MSK 10-053)]
+|2010-08-25 to 2013-07-23
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[#Selumetinib_monotherapy|Selumetinib]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycles'''
+</div></div>
+===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. [https://jamanetwork.com/journals/jama/fullarticle/1881312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24938562/ PubMed] [https://clinicaltrials.gov/study/NCT01143402 NCT01143402]
+==Fotemustine monotherapy {{#subobject:92d0c6|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:ff4f50|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433517/ Leyvraz et al. 2014 (EORTC 18021)]
+|2005-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Fotemustine_monotherapy|Fotemustine]]; HAI
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Fotemustine (Muphoran)]] as follows:
+**Cycle 1: 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+**Cycle 2 onwards: 100 mg/m<sup>2</sup> IV once on day 1
+'''8-week course, then 21-day cycles'''
+</div></div>
+===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. [https://doi.org/10.1093/annonc/mdt585 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433517/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24510314/ PubMed] [https://clinicaltrials.gov/study/NCT00110123 NCT00110123]
+==Ipilimumab & Nivolumab {{#subobject:51gu10|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:3a48jc|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8257877/ Pelster et al. 2020 (MDACC 2011-0919)]
+|2015-07-07 to 2018-03-07
+| style="background-color:#91cf61" |Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====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)'''
+</div></div>
 ===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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] NCT03070392
+# '''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. [https://doi.org/10.1200/JCO.20.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8257877/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33125309/ PubMed] [https://clinicaltrials.gov/study/NCT01585194 NCT01585194]
 ==TACE monotherapy {{#subobject:f96a1b|Regimen=1}}==
 TACE: '''<u>T</u>'''rans-'''<u>A</u>'''rterial '''<u>C</u>'''hemo-'''<u>E</u>'''mbolization
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:93050b|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://jamanetwork.com/journals/jama/article-abstract/373516 Mavligit et al. 1988]
+|[https://doi.org/10.1001/jama.1988.03410070102037 Mavligit et al. 1988]
+|1983-11 to 1987-04
 | style="background-color:#91cf61" |Non-randomized
 |-
 |}
-====Chemotherapy====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Local therapy====
 *[[TACE]]
 '''1 or more treatments'''
+</div></div>
 ===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. [https://jamanetwork.com/journals/jama/article-abstract/373516 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3398202 PubMed]
+# 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. [https://doi.org/10.1001/jama.1988.03410070102037 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3398202/ PubMed]
 ==Selumetinib monotherapy {{#subobject:4e8yua|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6e73a5|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 228: / Line 322: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ Carvajal et al. 2014 (MSK 10-053)]
-|2010-2013
+|2010-08-25 to 2013-07-23
 |style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ooc)
-|1. [[#Dacarbazine_monotherapy|Dacarbazine]]<br> 2. [[#Temozolomide_monotherapy|Temozolomide]]
+|1a. [[#Dacarbazine_monotherapy_2|Dacarbazine]]<br>1b. [[#Temozolomide_monotherapy|Temozolomide]]
-| style="background-color:#d9ef8b" |Might have superior OS
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 15.9 vs 7 wk<br>(HR 0.46, 95% CI 0.30-0.71)
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Selumetinib (Koselugo)]] 75 mg PO twice per day
 '''Continued indefinitely'''
+</div></div>
 ===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. [https://jamanetwork.com/journals/jama/fullarticle/1881312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24938562 PubMed] NCT01143402
+# '''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. [https://jamanetwork.com/journals/jama/fullarticle/1881312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24938562/ PubMed] [https://clinicaltrials.gov/study/NCT01143402 NCT01143402]
-==Tebentafusp monotherapy {{#subobject:4ugh17|Regimen=1}}==
-===Regimen {{#subobject:6eug88|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1056/nejmoa2103485 Nathan et al. 2021 (IMCgp100-202)]
-|2017-2020
-|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
-|Investigator's choice of:<br>1. [[#Dacarbazine_monotherapy|Dacarbazine]]<br>2. [[#Ipilimumab_monotherapy|Ipilimumab]]<br>3. [[#Pembrolizumab_monotherapy|Pembrolizumab]]
-| style="background-color:#1a9850" |Superior OS<br>OS12: 73% vs 59%<br>(HR 0.51, 95% CI 0.37-0.71)
-|-
-|}
-====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. [https://doi.org/10.1056/nejmoa2103485 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34551229/ PubMed] NCT03070392
 ==Temozolomide monotherapy {{#subobject:4e2652|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6e73a5|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 285: / Line 350: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ Carvajal et al. 2014 (MSK 10-053)]
-|2010-2013
+|2010-08-25 to 2013-07-23
 |style="background-color:#1a9851"|Randomized Phase 2 (C)
 |[[#Selumetinib_monotherapy|Selumetinib]]
-| style="background-color:#fee08b" |Might have inferior OS
+| style="background-color:#d73027" |Inferior PFS
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*MSK 10-053: No prior therapy with a MEK inhibitor, temozolomide, or dacarbazine
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
 '''28-day cycles'''
+</div></div>
 ===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. [https://jamanetwork.com/journals/jama/fullarticle/1881312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24938562 PubMed] NCT01143402
+# '''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. [https://jamanetwork.com/journals/jama/fullarticle/1881312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24938562/ PubMed] [https://clinicaltrials.gov/study/NCT01143402 NCT01143402]
 ==TILs {{#subobject:f33e1b|Regimen=1}}==
 TILs: '''<u>T</u>'''umor '''<u>I</u>'''filtrating '''<u>L</u>'''ymphocyte'''<u>s</u>'''
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:12350b|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490083/ Chandran et al. 2017 (NCI 13-C-0093)]
+|2013-06-07 to 2016-07-14
 | style="background-color:#91cf61" |Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[Autologous_HSCT#FC|FC]] lymphodepletion
+*[[Chimeric_antigen_receptor_T_cells_(CAR-T)#Cyclophosphamide_.26_Fludarabine_.28FC.29|FC]] lymphodepletion
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
-*[[Autologous TILs]]
+*Autologous [[:Category:Tumor infiltrating lymphocytes|TILs]]
+</div></div>
 ===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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30251-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490083/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28395880 PubMed] NCT01814046
+# '''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. [https://doi.org/10.1016/S1470-2045(17)30251-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490083/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28395880/ PubMed] [https://clinicaltrials.gov/study/NCT01814046 NCT01814046]
 [[Category:Uveal melanoma regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Skin cancers]]

Difference between revisions of "Uveal melanoma"

Revision as of 12:08, 23 June 2024

Guidelines

NCCN

Metastatic or unresectable disease, untreated

Dacarbazine monotherapy

Regimen

Chemotherapy

References

Ipilimumab monotherapy

Regimen

Immunotherapy

References

Ipilimumab & Nivolumab

Regimen

Immunotherapy

References

Melphalan isolated hepatic perfusion

Regimen

Chemotherapy

References

Pembrolizumab monotherapy

Regimen variant #1, weight-based

Immunotherapy

Regimen variant #2, flat dosing

Immunotherapy

References

Tebentafusp monotherapy

Regimen

Immunotherapy

References

Metastatic or unresectable disease, all lines of therapy

Dacarbazine monotherapy

Regimen

Prior treatment criteria

Chemotherapy

References

Fotemustine monotherapy

Regimen

Chemotherapy

References

Ipilimumab & Nivolumab

Regimen

Immunotherapy

References

TACE monotherapy

Regimen

Local therapy

References

Selumetinib monotherapy

Regimen

Prior treatment criteria

Targeted therapy

References

Temozolomide monotherapy

Regimen

Prior treatment criteria

Chemotherapy

References

TILs

Regimen

Preceding treatment

Immunotherapy

References

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