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A Phase II Study Of Sorafenib In Malignant Mesothelioma: Results Of Cancer And Leukemia Group B 30307

S. Dubey, P. Jänne, L. Krug, H. Pang, X. Wang, R. Heinze, C. Watt, J. Crawford, R. Kratzke, E. Vokes, H. Kindler
Published 2010 · Medicine

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Hypothesis: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. Methods: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. Results: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3–16.6%]), and 27 (54% [95% confidence interval = 39.3–68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). Conclusion: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted.
This paper references
10.1016/j.lungcan.2008.04.001
The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma.
J. Stebbing (2009)
10.1016/S0169-5002(05)80896-7
P-403 Vatalanib in patients with previously untreated advanced malignant mesothelioma (MM): Preliminary analysis of a phase II study by the Cancer and Leukemia Group B (CALGB 30107)
T. Jahan (2005)
10.1016/S0169-5002(03)91684-9
O-26 Thalidomide alone or in combination with cisplatin/Gemcitabine in malignant pleural mesothelioma (MM); Interim results from two parallel non randomized phase II studies
N. Pavlakis (2003)
10.1158/1535-7163.MCT-07-0052
Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion
A. Tsao (2007)
10.1056/NEJMc081780
Sorafenib in advanced hepatocellular carcinoma.
G. Spinzi (2008)
10.1200/JCO.2008.26.15_SUPPL.8063
Phase II study of sunitinib as second-line therapy in malignant pleural mesothelioma (MPM)
A. Nowak (2008)
Platelet-derived growth factor (PDGF) BB acts as a chemoattractant for human malignant mesothelioma cells via PDGF receptor beta-integrin alpha3beta1 interaction.
J. Klominek (1998)
10.3816/CLC.2006.N.003
Potential role of histone deacetylase inhibitors in mesothelioma: clinical experience with suberoylanilide hydroxamic acid.
L. Krug (2006)
10.1056/NEJMOA060655
Sorafenib in advanced clear-cell renal-cell carcinoma.
B. Escudier (2007)
10.1200/JCO.2000.18.23.3912
Phase II study of vinorelbine in patients with malignant pleural mesothelioma.
J. Steele (2000)
10.1200/JCO.2002.10.088
Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy.
H. Dvorak (2002)
10.1200/JCO.20005.14.589
Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada.
J. Van Meerbeeck (2005)
10.1038/sj.onc.1202527
VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells
T. Takahashi (1999)
10.1200/JCO.2005.01.3441
Phase II study of sorafenib in patients with advanced hepatocellular carcinoma.
G. Abou-Alfa (2006)
10.1200/JCO.2007.25.18_SUPPL.7526
Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM)
T. Karrison (2007)
Thalidomide alone or in combination with cisplatin/gemcitabine in malignant pleural mesothelioma: interim results from two parallel non randomized phase II studies. Lung cancer
N Pavlakis (2003)
10.1158/0008-5472.CAN-04-1443
BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis
S. Wilhelm (2004)
10.1002/path.824
Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma
L. Strizzi (2001)
Thalidomide alone or in combination with cisplatin/gemcitabine in malignant pleural mesothelioma: interim results from two parallel non randomized phase II studies
N Pavlakis (2003)
10.6004/JNCCN.2012.0006
[Malignant pleural mesothelioma].
Q. Kong (1983)
10.1200/JCO.2003.11.136
Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
N. Vogelzang (2003)
10.1016/J.CANLET.2005.08.010
Molecular pathways in malignant pleural mesothelioma.
B. Whitson (2006)
10.1016/S0169-5002(00)00166-5
Gemcitabine for malignant mesothelioma: A phase II trial by the Cancer and Leukemia Group B.
H. Kindler (2001)
10.1038/sj.bjc.6690650
VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours
Y. Ohta (1999)
10.1634/THEONCOLOGIST.12-1-20
Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) Program.
M. Hayat (2007)
A phase II study of novel oral antiangiogenic agent AZD2171 (NSC-732208) in malignant pleural mesothelioma
LL Garland (2009)
10.1016/j.ejca.2009.04.028
A prognostic index for progression-free survival in malignant mesothelioma with application to the design of phase II trials: a combined analysis of 10 EORTC trials.
J. Francart (2009)
10.1093/ANNONC/MDH059
Modified RECIST criteria for assessment of response in malignant pleural mesothelioma.
M. Byrne (2004)
SU5416 in malignant mesothelioma: a University of Chicago phase II consortium study
HL Kindler (2001)
10.1200/jco.2009.27.15_suppl.7511
SWOG S0509: A phase II study of novel oral antiangiogenic agent AZD2171 (NSC-732208) in malignant pleural mesothelioma.
L. Garland (2009)
10.1016/J.LUNGCAN.2004.10.005
Thalidomide in patients with malignant pleural mesothelioma.
P. Baas (2005)
Human malignant mesothelioma cell lines express PDGF beta-receptors whereas cultured normal mesothelial cells express predominantly PDGF alpha-receptors.
M. Versnel (1991)



This paper is referenced by
Nintedanib : new treatment for malignant pleural mesothelioma
(2017)
10.1080/14656566.2016.1176145
Advances in treatment of mesothelioma
C. Maggioni (2016)
10.1016/j.tips.2011.03.011
Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma.
R. Favoni (2011)
10.1016/j.lungcan.2012.06.011
Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium.
N. Campbell (2012)
10.6004/JNCCN.2012.0007
Novel therapies in phase II and III trials for malignant pleural mesothelioma.
M. Zauderer (2012)
10.1517/13543784.2012.681641
Anti-angiogenic therapies for malignant pleural mesothelioma
G. Ceresoli (2012)
10.1007/s11864-019-0616-7
Malignant Pleural Mesothelioma: Is Tailoring the Second-Line Therapy Really “Raising the Bar?”
V. Noia (2019)
A new standard for malignant pleural mesothelioma
Aneel Bhangu (2016)
Macrophages in Mesothelioma : Improving immunotherapy in pulmonary oncology
Sanne Lievense (2017)
10.1007/s10637-013-9993-0
Sorafenib plus dacarbazine in solid tumors: a phase I study with dynamic contrast-enhanced ultrasonography and genomic analysis of sequential tumor biopsy samples
V. Lazar (2013)
10.1097/CCO.0000000000000053
Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements
D. Christoph (2014)
10.1038/d41586-019-02218-y
Cancer-cell death ironed out
D. Fennell (2019)
Malignant Pleural Mesothelioma and the Role of Non – Operative Therapies Kelvin
C. Ng (2018)
10.3389/fonc.2020.00126
Antiangiogeneic Strategies in Mesothelioma
A. Nowak (2020)
10.1159/000339259
Malignant Pleural Mesothelioma: From the Bench to the Bedside
P. Astoul (2012)
10.1016/j.jtho.2018.08.2036
Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation
A. Tsao (2018)
10.1097/JTO.0b013e318248242c
Phase II Study of Dasatinib in Patients with Previously Treated Malignant Mesothelioma (Cancer and Leukemia Group B 30601): A Brief Report
A. Dudek (2012)
Dendritic cell-based immunotherapy in
R. Cornelissen (2012)
10.1007/978-3-319-53560-9_15
Standard Chemotherapy Options and Clinical Trials of Novel Agents for Mesothelioma
M. Zauderer (2017)
10.1053/j.seminoncol.2019.06.001
Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma.
A. Tsao (2019)
10.1371/journal.pbio.2000487
Inefficiencies and Patient Burdens in the Development of the Targeted Cancer Drug Sorafenib: A Systematic Review
James Mattina (2017)
10.1200/JCO.2017.72.9012
Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial.
F. Grosso (2017)
10.1097/JTO.0b013e31828c2b26
Phase 2 Study of Sorafenib in Malignant Mesothelioma Previously Treated with Platinum-Containing Chemotherapy
S. Papa (2013)
10.1016/j.ctrv.2012.12.005
Malignant mesothelioma: new insights into a rare disease.
J. Remon (2013)
10.1080/14737140.2016.1244008
Targeting the vasculature: anti-angiogenic agents for malignant mesothelioma
P. L. Chia (2016)
10.1016/j.lungcan.2015.06.018
Second line therapy in malignant pleural mesothelioma: A systematic review.
W. Buikhuisen (2015)
10.1016/j.ccm.2012.12.005
Malignant pleural mesothelioma: update on treatment options with a focus on novel therapies.
A. Haas (2013)
10.1055/s-0039-1693406
Malignant Mesothelioma: Has Anything Changed?
Roger Y Kim (2019)
10.1038/s41586-019-1426-6
Intercellular interaction dictates cancer cell ferroptosis via Merlin-YAP signalling
J. Wu (2019)
10.2217/LMT.14.17
Second-line treatment in malignant pleural mesothelioma: translating the evidence into clinical practice
G. Ceresoli (2014)
10.1097/JTO.0b013e3182333df5
Brief Report: A Phase II Study of Sunitinib in Malignant Pleural Mesothelioma. The NCIC Clinical Trials Group
S. Laurie (2011)
10.1016/j.jtho.2016.05.020
The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing
Marieke Hylebos (2016)
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