Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer.
<h4>Purpose</h4>Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0134731 |
| _version_ | 1830131226125533184 |
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| author | Yelena Y Janjigian Efsevia Vakiani Geoffrey Y Ku Jessica M Herrera Laura H Tang Nancy Bouvier Agnès Viale Nicholas D Socci Marinela Capanu Michael Berger David H Ilson |
| author_facet | Yelena Y Janjigian Efsevia Vakiani Geoffrey Y Ku Jessica M Herrera Laura H Tang Nancy Bouvier Agnès Viale Nicholas D Socci Marinela Capanu Michael Berger David H Ilson |
| author_sort | Yelena Y Janjigian |
| collection | DOAJ |
| description | <h4>Purpose</h4>Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer.<h4>Patients and methods</h4>This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity.<h4>Results</h4>Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET.<h4>Conclusion</h4>Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.<h4>Trial registration</h4>ClinicalTrials.gov NCT00917462. |
| first_indexed | 2024-12-17T06:11:52Z |
| format | Article |
| id | doaj.art-732f0d0655694c84a8d6a2f879728d29 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T06:11:52Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-732f0d0655694c84a8d6a2f879728d292022-12-21T22:00:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013473110.1371/journal.pone.0134731Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer.Yelena Y JanjigianEfsevia VakianiGeoffrey Y KuJessica M HerreraLaura H TangNancy BouvierAgnès VialeNicholas D SocciMarinela CapanuMichael BergerDavid H Ilson<h4>Purpose</h4>Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer.<h4>Patients and methods</h4>This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity.<h4>Results</h4>Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET.<h4>Conclusion</h4>Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.<h4>Trial registration</h4>ClinicalTrials.gov NCT00917462.https://doi.org/10.1371/journal.pone.0134731 |
| spellingShingle | Yelena Y Janjigian Efsevia Vakiani Geoffrey Y Ku Jessica M Herrera Laura H Tang Nancy Bouvier Agnès Viale Nicholas D Socci Marinela Capanu Michael Berger David H Ilson Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. PLoS ONE |
| title | Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. |
| title_full | Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. |
| title_fullStr | Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. |
| title_full_unstemmed | Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. |
| title_short | Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. |
| title_sort | phase ii trial of sorafenib in patients with chemotherapy refractory metastatic esophageal and gastroesophageal ge junction cancer |
| url | https://doi.org/10.1371/journal.pone.0134731 |
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