Eric J Sherman1,2, Lara A Dunn1,2, Heiko Schöder3, Alan L Ho1,2, Shrujal S Baxi1,2, Ronald A Ghossein4, Sofia S Haque3, Cami Sima5, Robert Michael Tuttle1,2, David G Pfister1,2. 1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 2. Department of Medicine, Weill Cornell Medicine, New York, New York. 3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract
BACKGROUND: Several multitargeted tyrosine kinase inhibitors (TKIs) have demonstrated activity in patients with thyroid cancer that is refractory to radioactive iodine (RAI). The antitumor effect is attributed at least in part to the ability of these TKIs to inhibit angiogenesis in these vascular tumors. Vascular endothelial growth factor (VEGF) Trap (VT) is a recombinantly produced fusion protein consisting solely of human sequences for VEGF receptors 1 and 2 extracellular domains and human immunoglobulin 1. Evaluating VT in patients with thyroid cancer is reasonable considering the activity observed with TKIs targeting VEGF. METHODS: The current study was a single-institution, phase 2, Simon 2-stage design (21 to >41 patients) study based on the objective response rate and/or 6-month progression-free survival as the primary endpoints. Eligible patients were required to have progressive, RAI-refractory and/or [18 F]fludeoxyglucose-avid, recurrent and/or metastatic, nonmedullary, nonanaplastic thyroid cancer; disease that was measurable using Response Evaluation Criteria In Solid Tumors (RECIST) criteria; and adequate organ and bone marrow function. VT at a dose of 4 mg/kg intravenously was administered every 14 days. RESULTS: A total of 40 patients were included in the analysis. Of these patients, 24 had papillary thyroid cancer, 2 had follicular thyroid cancer, and 11 had Hurthle cell thyroid cancer. The final 3 tumors were classified as poorly differentiated. There were no complete and/or partial responses noted; 34 patients achieved stable disease and 6 patients experienced disease progression as their best response. Of the 34 patients with stable disease, 16 remained on the study for >6 months and 6 patients remained on the study for >12 months. The median duration on treatment was 4.1 months (range, 0.6-30.8 months). CONCLUSIONS: Unlike TKIs, which have shown responses in this setting, to the authors' knowledge there have been no responses observed with the use of single-agent VT to date. It does not appear to be a promising drug for the treatment of patients with thyroid cancer.
BACKGROUND: Several multitargeted tyrosine kinase inhibitors (TKIs) have demonstrated activity in patients with thyroid cancer that is refractory to radioactive iodine (RAI). The antitumor effect is attributed at least in part to the ability of these TKIs to inhibit angiogenesis in these vascular tumors. Vascular endothelial growth factor (VEGF) Trap (VT) is a recombinantly produced fusion protein consisting solely of human sequences for VEGF receptors 1 and 2 extracellular domains and human immunoglobulin 1. Evaluating VT in patients with thyroid cancer is reasonable considering the activity observed with TKIs targeting VEGF. METHODS: The current study was a single-institution, phase 2, Simon 2-stage design (21 to >41 patients) study based on the objective response rate and/or 6-month progression-free survival as the primary endpoints. Eligible patients were required to have progressive, RAI-refractory and/or [18 F]fludeoxyglucose-avid, recurrent and/or metastatic, nonmedullary, nonanaplastic thyroid cancer; disease that was measurable using Response Evaluation Criteria In Solid Tumors (RECIST) criteria; and adequate organ and bone marrow function. VT at a dose of 4 mg/kg intravenously was administered every 14 days. RESULTS: A total of 40 patients were included in the analysis. Of these patients, 24 had papillary thyroid cancer, 2 had follicular thyroid cancer, and 11 had Hurthle cell thyroid cancer. The final 3 tumors were classified as poorly differentiated. There were no complete and/or partial responses noted; 34 patients achieved stable disease and 6 patients experienced disease progression as their best response. Of the 34 patients with stable disease, 16 remained on the study for >6 months and 6 patients remained on the study for >12 months. The median duration on treatment was 4.1 months (range, 0.6-30.8 months). CONCLUSIONS: Unlike TKIs, which have shown responses in this setting, to the authors' knowledge there have been no responses observed with the use of single-agent VT to date. It does not appear to be a promising drug for the treatment of patients with thyroid cancer.
Authors: M Klein; E Picard; J M Vignaud; B Marie; L Bresler; B Toussaint; G Weryha; A Duprez; J Leclère Journal: J Endocrinol Date: 1999-04 Impact factor: 4.286
Authors: Maher N Younes; Yasemin D Yazici; Seungwon Kim; Samar A Jasser; Adel K El-Naggar; Jeffrey N Myers Journal: Clin Cancer Res Date: 2006-06-01 Impact factor: 12.531
Authors: Jocelyn Holash; Sam Davis; Nick Papadopoulos; Susan D Croll; Lillian Ho; Michelle Russell; Patricia Boland; Ray Leidich; Donna Hylton; Elena Burova; Ella Ioffe; Tammy Huang; Czeslaw Radziejewski; Kevin Bailey; James P Fandl; Tom Daly; Stanley J Wiegand; George D Yancopoulos; John S Rudge Journal: Proc Natl Acad Sci U S A Date: 2002-08-12 Impact factor: 11.205
Authors: Scott M Wilhelm; Lila Adnane; Philippa Newell; Augusto Villanueva; Josep M Llovet; Mark Lynch Journal: Mol Cancer Ther Date: 2008-10 Impact factor: 6.261
Authors: Andrew J Bauer; Richard Terrell; Nalinikrishna K Doniparthi; Aneeta Patel; R Michael Tuttle; Motoyasu Saji; Matthew D Ringel; Gary L Francis Journal: Thyroid Date: 2002-11 Impact factor: 6.568
Authors: Steven I Sherman; Lori J Wirth; Jean-Pierre Droz; Michael Hofmann; Lars Bastholt; Renato G Martins; Lisa Licitra; Michael J Eschenberg; Yu-Nien Sun; Todd Juan; Daniel E Stepan; Martin J Schlumberger Journal: N Engl J Med Date: 2008-07-03 Impact factor: 91.245
Authors: Vandana Gupta-Abramson; Andrea B Troxel; Anoma Nellore; Kanchan Puttaswamy; Maryann Redlinger; Kathy Ransone; Susan J Mandel; Keith T Flaherty; Laurie A Loevner; Peter J O'Dwyer; Marcia S Brose Journal: J Clin Oncol Date: 2008-06-09 Impact factor: 44.544
Authors: Christopher N Prichard; Seungwon Kim; Yasmin D Yazici; Dao D Doan; Samar A Jasser; Mahitosh Mandal; Jeffrey N Myers Journal: Laryngoscope Date: 2007-04 Impact factor: 3.325
Authors: Nicholas Papadopoulos; Joel Martin; Qin Ruan; Ashique Rafique; Michael P Rosconi; Ergang Shi; Erica A Pyles; George D Yancopoulos; Neil Stahl; Stanley J Wiegand Journal: Angiogenesis Date: 2012-06 Impact factor: 9.596
Authors: Sophie Leboulleux; Lars Bastholt; Thomas Krause; Christelle de la Fouchardiere; Jan Tennvall; Ahmad Awada; José Manuel Gómez; Françoise Bonichon; Laurence Leenhardt; Christine Soufflet; Muriel Licour; Martin J Schlumberger Journal: Lancet Oncol Date: 2012-08-14 Impact factor: 41.316
Authors: Flávia Melo Cunha de Pinho Pessoa; Caio Bezerra Machado; Emerson Lucena da Silva; Laudreísa da Costa Pantoja; Rodrigo Monteiro Ribeiro; Maria Elisabete Amaral de Moraes; Manoel Odorico de Moraes Filho; Raquel Carvalho Montenegro; André Salim Khayat; Caroline Aquino Moreira-Nunes Journal: Int J Mol Sci Date: 2022-03-30 Impact factor: 5.923
Authors: Mary E Kelley; Ki Sueng Choi; Justin K Rajendra; W Edward Craighead; Jeffrey J Rakofsky; Boadie W Dunlop; Helen S Mayberg Journal: Biol Psychiatry Date: 2021-02-26 Impact factor: 12.810