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Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-care Chemotherapy In Patients With Advanced Melanoma.

A. Ribas, R. Kefford, M. A. Marshall, C. Punt, J. Haanen, M. Mármol, C. Garbe, H. Gogas, J. Schachter, G. Linette, P. Lorigan, K. Kendra, M. Maio, U. Trefzer, M. Smylie, G. McArthur, B. Dréno, P. D. Nathan, J. Mackiewicz, J. Kirkwood, J. Gomez-Navarro, B. Huang, D. Pavlov, A. Hauschild
Published 2013 · Medicine, Mathematics

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PURPOSE 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.
This paper references
10.1200/JCO.1999.17.7.2105
High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993.
M. Atkins (1999)
10.1200/JCO.2010.28.18_SUPPL.4
A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 peptide vaccine and the combination in patients with previously treated, unresectable stage III or IV melanoma.
S. O'Day (2010)
10.1093/jnci/92.3.205
New Guidelines to Evaluate the Response to Treatment in Solid Tumors.
P. Therasse (2000)
10.1200/JCO.2000.18.1.158
Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.
M. Middleton (2000)
10.1158/1078-0432.CCR-09-2033
Phase II Trial of Tremelimumab (CP-675,206) in Patients with Advanced Refractory or Relapsed Melanoma
J. Kirkwood (2010)
10.1056/NEJMoa1003466
Improved survival with ipilimumab in patients with metastatic melanoma.
F. S. Hodi (2010)
10.1200/JCO.2005.01.109
Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206.
A. Ribas (2005)
10.1634/THEONCOLOGIST.12-7-873
Tremelimumab (CP-675,206), a cytotoxic T lymphocyte associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancer.
A. Ribas (2007)
10.1200/JCO.2010.28.15_SUPPL.8509
Re-induction with ipilimumab, gp100 peptide vaccine, or a combination of both from a phase III, randomized, double-blind, multicenter study of previously treated patients with unresectable stage III or IV melanoma.
F. S. Hodi (2010)
10.1056/NEJMoa1104621
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
C. Robert (2011)
10.1007/BF02967383
New guidelines to evaluate the response to treatment in solid tumors
P. Therasse (2000)
10.1200/JCO.2010.30.7280
Prognostic significance of molecular remission in follicular lymphoma.
U. Dührsen (2010)
10.1200/JCO.2006.24.18_SUPPL.2542
Ex vivo blood stimulation assay as a translational research tool in the development of the ticilimumab (CP-675,206).
R. Millham (2006)
10.1200/JCO.2008.19.2435
Phase I/II trial of tremelimumab in patients with metastatic melanoma.
L. Camacho (2009)
10.1093/annonc/mdq013
Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.
S. O’Day (2010)



This paper is referenced by
10.2147/DDDT.S115493
Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis
X. Zhang (2016)
10.3390/toxins6030914
Immune Checkpoint Blockade in Cancer Treatment: A Double-Edged Sword Cross-Targeting the Host as an “Innocent Bystander”
L. Gelao (2014)
Novel adenoviral vaccine encoding multiple tumor neo-antigens in combination with checkpoint blockade as a strategy for more effective cancer treatment
M. D. Lucia (2018)
10.1186/1752-1947-8-240
Serious haematological toxicity during and after ipilimumab treatment: a case series
E. Simeone (2014)
10.1007/s00280-019-03894-3
Cancer immunotherapy: the art of targeting the tumor immune microenvironment
J. L. da Silva (2019)
10.1007/978-981-15-3266-5_5
Mechanisms of Resistance to Checkpoint Blockade Therapy.
Hubing Shi (2020)
10.1007/978-1-4939-7193-0_71
Precision medicine based on next-generation sequencing and master controllers
K. Dukleska (2018)
10.3390/molecules24183214
Sex Differences in Cancer Immunotherapy Efficacy, Biomarkers, and Therapeutic Strategy
S. Wang (2019)
10.2169/internalmedicine.1011-18
Bicytopenia in Primary Lung Melanoma Treated with Nivolumab
A. Takahashi (2019)
10.1053/j.seminoncol.2014.09.003
Current perspectives on immunotherapy.
J. Weber (2014)
10.1136/esmoopen-2019-000510
New emerging targets in cancer immunotherapy: the role of Cluster of Differentiation 40 (CD40/TNFR5)
M. Piechutta (2019)
10.1111/cen.13063
Immune checkpoint inhibitor‐related hypophysitis and endocrine dysfunction: clinical review
M. Joshi (2016)
10.1080/2162402X.2015.1008814
Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications
A. Buqué (2015)
10.1007/978-3-662-46410-6_1
Cancer Immunotherapy Confers a Global Benefit
Z. Aryan (2015)
10.1186/s40425-016-0172-7
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one
A. Lundqvist (2016)
10.1007/s11910-014-0440-1
Microenvironmental Clues for Glioma Immunotherapy
M. Platten (2014)
10.1053/j.seminoncol.2015.02.001
Immune checkpoint blockade in malignant mesothelioma.
Luana Calabrò (2015)
10.1159/000478081
Adverse Reactions to Biologics: Melanoma (Ipilimumab, Nivolumab, Pembrolizumab).
S. Hwang (2018)
10.1007/s40290-020-00326-z
Addressing Recent Failures in Immuno-Oncology Trials to Guide Novel Immunotherapeutic Treatment Strategies
Shazia K. Nakhoda (2020)
10.1016/j.ctrv.2019.02.001
Network meta-analysis of therapies for previously untreated advanced BRAF-mutated melanoma.
Michael J. Zoratti (2019)
10.1038/bjc.2013.227
Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours
MichaelJ. Millward (2013)
10.1016/j.molimm.2015.01.025
Clinical deployment of antibodies for treatment of melanoma.
B. Curti (2015)
10.18632/oncotarget.4375
Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials
Ruiqin Mai (2015)
10.1016/j.addr.2014.09.007
Targeting myeloid cells using nanoparticles to improve cancer immunotherapy.
Z. Amoozgar (2015)
10.3390/cancers7030830
The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options
E. Gabriel (2015)
10.1007/s11060-015-1747-8
The role of checkpoints in the treatment of GBM
J. E. Kim (2015)
10.21007/ETD.CGHS.2017.0446
Discovery of Novel Tubulin Inhibitors and Selective Survivin Inhibitors for Advanced Melanoma and Total Synthesis of Bioactive 20S-hydroxyvitamin D3
Qinghui Wang (2017)
10.1001/jamanetworkopen.2019.3433
Correlation of Milestone Restricted Mean Survival Time Ratio With Overall Survival Hazard Ratio in Randomized Clinical Trials of Immune Checkpoint Inhibitors
Zi-Xian Wang (2019)
10.1158/1078-0432.CCR-18-1550
Immunotherapy of Melanoma: Facts and Hopes
S. Weiss (2019)
10.4155/CLI.14.102
Cancer therapy with Newcastle disease virus: rationale for new immunotherapeutic combinations
Tamar Plitt (2015)
10.1016/j.wneu.2017.03.011
Biomarkers and Immunotherapeutic Targets in Glioblastoma.
A. Hung (2017)
10.1016/j.wneu.2017.01.101
Peri-SRS Administration of Immune Checkpoint Therapy for Melanoma Metastatic to the Brain: Investigating Efficacy and the Effects of Relative Treatment Timing on Lesion Response.
M. Yusuf (2017)
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