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dc.contributor.authorRibas, A
dc.contributor.authorKefford, R
dc.contributor.authorMarshall, M
dc.contributor.authorPunt, C
dc.contributor.authorHaanen, J
dc.contributor.authorMarmol, M
dc.contributor.authorGarbe, C
dc.contributor.authorGogas, H
dc.contributor.authorSchachter, J
dc.contributor.authorLinette, G
dc.contributor.authorLorigan, Paul C
dc.contributor.authorKendra, K
dc.contributor.authorMaio, M
dc.contributor.authorTrefzer, U
dc.contributor.authorSmylie, M
dc.contributor.authorMcArthur, G
dc.contributor.authorDreno, B
dc.contributor.authorNathan, P
dc.contributor.authorMackiewicz, J
dc.contributor.authorKirkwood, J
dc.contributor.authorGomez-Navarro, J
dc.contributor.authorHuang, B
dc.contributor.authorPavlov, D
dc.contributor.authorHauschild, A
dc.date.accessioned2013-03-22T14:02:23Z
dc.date.available2013-03-22T14:02:23Z
dc.date.issued2013-02-10
dc.identifier.citationPhase III randomized clinical trial comparing Tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. 2013, 31 (5):616-22 J Clin Oncolen_GB
dc.identifier.issn1527-7755
dc.identifier.pmid23295794
dc.identifier.doi10.1200/JCO.2012.44.6112
dc.identifier.urihttp://hdl.handle.net/10541/275687
dc.description.abstractPURPOSE In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. PATIENTS AND METHODS Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. CONCLUSION This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.
dc.language.isoenen
dc.rightsArchived with thanks to Journal of clinical oncology : official journal of the American Society of Clinical Oncologyen_GB
dc.titlePhase III randomized clinical trial comparing Tremelimumab with standard-of-care chemotherapy in patients with advanced melanomaen
dc.typeArticleen
dc.contributor.departmentDivision of Hematology-Oncology, 11-934 Factor Building, UCLA Medical Center, 10833 Le Conte Ave, Los Angeles, CA 90095-1782; aribas@mednet.ucla.edu.en_GB
dc.identifier.journalJournal of Clinical Oncologyen_GB
html.description.abstractPURPOSE In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. PATIENTS AND METHODS Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. CONCLUSION This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.


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