Phase II trial of sorafenib in patients with chemotherapy refractory metastatic esophageal and gastroesophageal (GE) junction cancer Journal Article


Authors: Janjigian, Y. Y.; Vakiani, E.; Ku, G. Y.; Herrera, J. M.; Tang, L. H.; Bouvier, N.; Viale, A.; Socci, N. D.; Capanu, M.; Berger, M.; Ilson, D. H.
Article Title: Phase II trial of sorafenib in patients with chemotherapy refractory metastatic esophageal and gastroesophageal (GE) junction cancer
Abstract: Purpose: 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. Patients and Methods 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. Results 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. Conclusion Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer. © 2015 Janjigian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: immunohistochemistry; adult; cancer survival; clinical article; controlled study; human tissue; protein expression; protein phosphorylation; treatment response; gene mutation; gene sequence; overall survival; fatigue; sorafenib; diarrhea; drug dose reduction; drug efficacy; drug safety; hypertension; skin toxicity; anorexia; progression free survival; phase 2 clinical trial; gene amplification; mucosa inflammation; nausea; vomiting; dehydration; weight reduction; platelet derived growth factor receptor; vasculotropin receptor 2; alanine aminotransferase blood level; aspartate aminotransferase blood level; asthenia; rash; oncogene; aspartate aminotransferase; malaise; disease severity; acne; esophagus cancer; hand foot syndrome; dry skin; lethargy; alopecia; pik3ca gene; gastroesophageal junction cancer; hmga2 gene; tp53 gene; met gene; next generation sequencing; exome; esophagus fistula; arid1a gene; human; male; female; article; metastatic chemotherapy refractory esophageal cancer
Journal Title: PLoS ONE
Volume: 10
Issue: 8
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2015-08-14
Start Page: e0134731
Language: English
DOI: 10.1371/journal.pone.0134731
PROVIDER: scopus
PMCID: PMC4537304
PUBMED: 26275293
DOI/URL:
Notes: Export Date: 2 November 2015 -- Source: Scopus
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MSK Authors
  1. Geoffrey Yuyat Ku
    125 Ku
  2. Marinela Capanu
    265 Capanu
  3. Yelena Yuriy Janjigian
    194 Janjigian
  4. Laura Hong Tang
    358 Tang
  5. Agnes Viale
    216 Viale
  6. David H Ilson
    327 Ilson
  7. Nancy Bouvier
    38 Bouvier
  8. Nicholas D Socci
    202 Socci
  9. Michael Forman Berger
    501 Berger
  10. Efsevia Vakiani
    196 Vakiani