Difference between revisions of "Uveal melanoma"
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Warner-admin (talk | contribs) m (Text replacement - "=Guidelines=" to "=Guidelines= '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.'''") |
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*[https://www.nccn.org/professionals/physician_gls/pdf/uveal.pdf NCCN Guidelines - Melanoma: Uveal] | *[https://www.nccn.org/professionals/physician_gls/pdf/uveal.pdf NCCN Guidelines - Melanoma: Uveal] | ||
− | =Metastatic or unresectable disease= | + | =Metastatic or unresectable disease, untreated= |
− | ==Dacarbazine monotherapy {{#subobject: | + | ==Dacarbazine monotherapy {{#subobject:jg399b|Regimen=1}}== |
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen {{#subobject: | + | ===Regimen {{#subobject:bensyc|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
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!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
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|[https://doi.org/10.1200/JCO.2017.74.1090 Carvajal et al. 2018 (SUMIT)] | |[https://doi.org/10.1200/JCO.2017.74.1090 Carvajal et al. 2018 (SUMIT)] | ||
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|- | |- | ||
|} | |} | ||
+ | ''Note: prior nonsystemic therapy was allowed in SUMIT.'' | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
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</div></div> | </div></div> | ||
===References=== | ===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. [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] | # '''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] | # '''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] | ||
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==Ipilimumab monotherapy {{#subobject:dga21b|Regimen=1}}== | ==Ipilimumab monotherapy {{#subobject:dga21b|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
Line 106: | Line 73: | ||
===References=== | ===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] | # '''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: | + | ==Ipilimumab & Nivolumab {{#subobject:5jiw10|Regimen=1}}== |
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen | + | ===Regimen {{#subobject:3a481c|Variant=1}}=== |
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/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 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
Line 125: | Line 94: | ||
**Cycle 5 onwards: 3 mg/kg IV once on day 1 | **Cycle 5 onwards: 3 mg/kg IV once on day 1 | ||
'''21-day cycle for 4 cycles, then 14-day cycles''' | '''21-day cycle for 4 cycles, then 14-day cycles''' | ||
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</div></div> | </div></div> | ||
===References=== | ===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://doi.org/10.1200/JCO.20.00550 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33417511/ PubMed] [https://clinicaltrials.gov/study/NCT02626962 NCT02626962] | # '''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://doi.org/10.1200/JCO.20.00550 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33417511/ PubMed] [https://clinicaltrials.gov/study/NCT02626962 NCT02626962] | ||
− | + | ||
==Pembrolizumab monotherapy {{#subobject:dhuahb|Regimen=1}}== | ==Pembrolizumab monotherapy {{#subobject:dhuahb|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
Line 193: | Line 143: | ||
===References=== | ===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] | # '''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"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen {{#subobject: | + | ===Regimen {{#subobject:6eug88|Variant=1}}=== |
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="color:white; background-color:#404040" |
− | !style="width: | + | |<small>'''FDA-recommended dose'''</small> |
− | !style="width: | + | |- |
+ | |} | ||
+ | {| 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>]''' | ||
|- | |- | ||
− | |[ | + | |} --> |
− | | style="background-color:# | + | |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 (primary endpoint)<br>OS12: 73% vs 59%<br>(HR 0.51, 95% CI 0.37-0.71) | ||
|- | |- | ||
|} | |} | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <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> | </div></div> | ||
===References=== | ===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] |
− | == | + | =Metastatic or unresectable disease, all lines of therapy= |
+ | ==Dacarbazine monotherapy {{#subobject:d3599b|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen {{#subobject: | + | ===Regimen {{#subobject:bede4c|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
Line 223: | Line 190: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ Carvajal et al. 2014 (MSK 10-053)] | |[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 ( | + | |style="background-color:#1a9851"|Randomized Phase 2 (C) |
− | | | + | |[[#Selumetinib_monotherapy|Selumetinib]] |
− | | style="background-color:# | + | | 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: | ||
+ | **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''' | ||
+ | </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"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
− | ==== | + | ====Immunotherapy==== |
− | *[[ | + | *[[Ipilimumab (Yervoy)]] as follows: |
− | ''' | + | **Cycles 1 to 4: 1 mg/kg IV once on day 1 |
+ | *[[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''' | ||
</div></div> | </div></div> | ||
===References=== | ===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. [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] [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"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen {{#subobject: | + | ===Regimen {{#subobject:93050b|Variant=1}}=== |
− | {| class="wikitable" style=" | + | {| 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://doi.org/10.1001/jama.1988.03410070102037 Mavligit et al. 1988] | ||
+ | |NR in abstract | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <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://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;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
Line 251: | Line 290: | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[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 (E-switch-ooc) | |
− | |- | + | |1a. [[#Dacarbazine_monotherapy_2|Dacarbazine]]<br>1b. [[#Temozolomide_monotherapy|Temozolomide]] |
− | + | | 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) | |
− | |||
− | |style="background-color:#1a9851"|Phase | ||
− | | | ||
− | | style="background-color:#1a9850" |Superior | ||
|- | |- | ||
|} | |} | ||
+ | <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"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
− | ==== | + | ====Targeted therapy==== |
− | *[[ | + | *[[Selumetinib (Koselugo)]] 75 mg PO twice per day |
− | + | '''Continued indefinitely''' | |
− | |||
− | |||
− | ''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] [https://clinicaltrials.gov/study/NCT01143402 NCT01143402] |
− | |||
==Temozolomide monotherapy {{#subobject:4e2652|Regimen=1}}== | ==Temozolomide monotherapy {{#subobject:4e2652|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
Line 284: | Line 319: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249701/ Carvajal et al. 2014 (MSK 10-053)] | |[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) | |style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
|[[#Selumetinib_monotherapy|Selumetinib]] | |[[#Selumetinib_monotherapy|Selumetinib]] | ||
Line 290: | Line 325: | ||
|- | |- | ||
|} | |} | ||
+ | <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"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 301: | Line 340: | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:12350b|Variant=1}}=== | ===Regimen {{#subobject:12350b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !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)] | |[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 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- |
Revision as of 12:17, 29 October 2023
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.
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 article 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.
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 |
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 once on day 1
- Nivolumab (Opdivo) as follows:
- Cycles 1 to 4: 1 mg/kg IV once on day 1
- Cycle 5 onwards: 3 mg/kg IV 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. link to original article PubMed NCT02626962
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 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 OS (primary endpoint) OS12: 73% vs 59% (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. link to original article contains dosing details in manuscript PubMed NCT03070392
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 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:
- Weeks 1 to 3: 100 mg/m2 IV once per day on days 1, 8, 15
- Weeks 4 to 8: no treatment
- Week 9 onwards: 100 mg/m2 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. 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: 1 mg/kg IV once on day 1
- 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
- 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 PubMed NCT01585194
TACE monotherapy
TACE: Trans-Arterial Chemo-Embolization
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Mavligit et al. 1988 | NR in abstract | 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 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
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