Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma
Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in thes...
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| creator | Zimmer, Lisa Vaubel, Julia Mohr, Peter Hauschild, Axel Utikal, Jochen Simon, Jan Garbe, Claus Herbst, Rudolf Enk, Alexander Kämpgen, Eckhart Livingstone, Elisabeth Bluhm, Leonie Rompel, Rainer Griewank, Klaus G Fluck, Michael Schilling, Bastian Schadendorf, Dirk |
| description | Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.
We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.
Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1), median progression-free survival 2.8 months (95% CI 2.5-2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3-4 events (36%). One drug-related death due to pancytopenia was observed.
Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.
ClinicalTrials.gov NCT01355120. |
| doi_str_mv | 10.1371/journal.pone.0118564 |
| format | Article |
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We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.
Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1), median progression-free survival 2.8 months (95% CI 2.5-2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3-4 events (36%). One drug-related death due to pancytopenia was observed.
Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.
ClinicalTrials.gov NCT01355120.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0118564</identifier><identifier>PMID: 25761109</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - therapeutic use ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - therapeutic use ; Clinical trials ; Criteria ; Dermatology ; Disease control ; Dosage ; Female ; History, Ancient ; Humans ; Immunotherapy ; Ipilimumab ; Kaplan-Meier Estimate ; Kinases ; Life expectancy ; Lymphocytes ; Medical prognosis ; Medical treatment ; Melanoma ; Melanoma - drug therapy ; Melanoma - mortality ; Melanoma - secondary ; Metastases ; Metastasis ; Middle Aged ; Monoclonal antibodies ; Mutation ; Pancytopenia ; Patients ; Proportional Hazards Models ; Skin cancer ; Survival ; Targeted cancer therapy ; Toxicity ; Treatment Outcome ; Tumors ; Uveal Neoplasms - drug therapy ; Uveal Neoplasms - mortality ; Uveal Neoplasms - pathology</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0118564</ispartof><rights>2015 Zimmer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Zimmer et al 2015 Zimmer et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-de35acea1ad1317ab829fc6231dbc1a860646f5363198f70710ce62e769e11f03</citedby><cites>FETCH-LOGICAL-c526t-de35acea1ad1317ab829fc6231dbc1a860646f5363198f70710ce62e769e11f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356548/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356548/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25761109$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Perez-Gracia, Jose Luis</contributor><creatorcontrib>Zimmer, Lisa</creatorcontrib><creatorcontrib>Vaubel, Julia</creatorcontrib><creatorcontrib>Mohr, Peter</creatorcontrib><creatorcontrib>Hauschild, Axel</creatorcontrib><creatorcontrib>Utikal, Jochen</creatorcontrib><creatorcontrib>Simon, Jan</creatorcontrib><creatorcontrib>Garbe, Claus</creatorcontrib><creatorcontrib>Herbst, Rudolf</creatorcontrib><creatorcontrib>Enk, Alexander</creatorcontrib><creatorcontrib>Kämpgen, Eckhart</creatorcontrib><creatorcontrib>Livingstone, Elisabeth</creatorcontrib><creatorcontrib>Bluhm, Leonie</creatorcontrib><creatorcontrib>Rompel, Rainer</creatorcontrib><creatorcontrib>Griewank, Klaus G</creatorcontrib><creatorcontrib>Fluck, Michael</creatorcontrib><creatorcontrib>Schilling, Bastian</creatorcontrib><creatorcontrib>Schadendorf, Dirk</creatorcontrib><title>Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.
We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.
Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1), median progression-free survival 2.8 months (95% CI 2.5-2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3-4 events (36%). One drug-related death due to pancytopenia was observed.
Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.
ClinicalTrials.gov NCT01355120.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Clinical trials</subject><subject>Criteria</subject><subject>Dermatology</subject><subject>Disease control</subject><subject>Dosage</subject><subject>Female</subject><subject>History, Ancient</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Ipilimumab</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>Life expectancy</subject><subject>Lymphocytes</subject><subject>Medical prognosis</subject><subject>Medical treatment</subject><subject>Melanoma</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - mortality</subject><subject>Melanoma - secondary</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Mutation</subject><subject>Pancytopenia</subject><subject>Patients</subject><subject>Proportional Hazards Models</subject><subject>Skin cancer</subject><subject>Survival</subject><subject>Targeted cancer therapy</subject><subject>Toxicity</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Uveal Neoplasms - 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The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.
We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.
Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1), median progression-free survival 2.8 months (95% CI 2.5-2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3-4 events (36%). One drug-related death due to pancytopenia was observed.
Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.
ClinicalTrials.gov NCT01355120.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25761109</pmid><doi>10.1371/journal.pone.0118564</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-03, Vol.10 (3), p.e0118564 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1662426573 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Aged, 80 and over Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Clinical trials Criteria Dermatology Disease control Dosage Female History, Ancient Humans Immunotherapy Ipilimumab Kaplan-Meier Estimate Kinases Life expectancy Lymphocytes Medical prognosis Medical treatment Melanoma Melanoma - drug therapy Melanoma - mortality Melanoma - secondary Metastases Metastasis Middle Aged Monoclonal antibodies Mutation Pancytopenia Patients Proportional Hazards Models Skin cancer Survival Targeted cancer therapy Toxicity Treatment Outcome Tumors Uveal Neoplasms - drug therapy Uveal Neoplasms - mortality Uveal Neoplasms - pathology |
| title | Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T03%3A35%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Phase%20II%20DeCOG-study%20of%20ipilimumab%20in%20pretreated%20and%20treatment-na%C3%AFve%20patients%20with%20metastatic%20uveal%20melanoma&rft.jtitle=PloS%20one&rft.au=Zimmer,%20Lisa&rft.date=2015-03-11&rft.volume=10&rft.issue=3&rft.spage=e0118564&rft.pages=e0118564-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0118564&rft_dat=%3Cproquest_plos_%3E3621517241%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1662426573&rft_id=info:pmid/25761109&rft_doaj_id=oai_doaj_org_article_2ff3e96d807047c3a0d2ce8d8353dfe0&rfr_iscdi=true |