dc.contributor.author | Petty, RD | |
dc.contributor.author | Dahle-Smith, A | |
dc.contributor.author | Stevenson, DAJ | |
dc.contributor.author | Osborne, A | |
dc.contributor.author | Massie, D | |
dc.contributor.author | Clark, C | |
dc.contributor.author | Murray, GI | |
dc.contributor.author | Dutton, SJ | |
dc.contributor.author | Roberts, C | |
dc.contributor.author | Chong, IY | |
dc.contributor.author | Mansoor, W | |
dc.contributor.author | Thompson, J | |
dc.contributor.author | Harrison, M | |
dc.contributor.author | Chatterjee, A | |
dc.contributor.author | Falk, SJ | |
dc.contributor.author | Elyan, S | |
dc.contributor.author | Garcia-Alonso, A | |
dc.contributor.author | Fyfe, DW | |
dc.contributor.author | Wadsley, J | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Ferry, DR | |
dc.contributor.author | Miedzybrodzka, Z | |
dc.date.accessioned | 2017-11-28T12:12:48Z | |
dc.date.issued | 2017-07-10 | |
dc.identifier.citation | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017, 35 (20), pp. 2279 - 2287 | |
dc.identifier.issn | 0732-183X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/957 | |
dc.identifier.eissn | 1527-7755 | |
dc.identifier.doi | 10.1200/jco.2016.70.3934 | |
dc.description.abstract | Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status. EGFR CNG was determined by fluorescent in situ hybridization (FISH) using prespecified criteria and EGFR FISH-positive status was defined as high polysomy or amplification. Results Biomarker data were available for 340 patients. In EGFR FISH-positive tumors (20.2%), overall survival was improved with gefitinib compared with placebo (hazard ratio [HR] for death, 0.59; 95% CI, 0.35 to 1.00; P = .05). In EGFR FISH-negative tumors, there was no difference in overall survival with gefitinib compared with placebo (HR for death, 0.90; 95% CI, 0.69 to 1.18; P = .46). Patients with EGFR amplification (7.2%) gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI, 0.07 to 0.64; P = .006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF, and PIK3CA mutations, or for any mutation versus none. Conclusion EGFR CNG assessed by FISH appears to identify a subgroup of patients with esophageal cancer who may benefit from gefitinib as a second-line treatment. Results of this study suggest that anti-EGFR therapies should be investigated in prospective clinical trials in different settings in EGFR FISH-positive and, in particular, EGFR-amplified esophageal cancer. | |
dc.format | Print-Electronic | |
dc.format.extent | 2279 - 2287 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Esophageal Neoplasms | |
dc.subject | Quinazolines | |
dc.subject | Proto-Oncogene Proteins B-raf | |
dc.subject | Receptor, Epidermal Growth Factor | |
dc.subject | Antineoplastic Agents | |
dc.subject | In Situ Hybridization, Fluorescence | |
dc.subject | Survival Rate | |
dc.subject | Single-Blind Method | |
dc.subject | DNA Mutational Analysis | |
dc.subject | Signal Transduction | |
dc.subject | Gene Amplification | |
dc.subject | Gene Dosage | |
dc.subject | Mutation | |
dc.subject | Genes, erbB-1 | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Proto-Oncogene Proteins p21(ras) | |
dc.subject | Randomized Controlled Trials as Topic | |
dc.subject | Clinical Trials, Phase III as Topic | |
dc.subject | Phosphatidylinositol 3-Kinases | |
dc.subject | Class I Phosphatidylinositol 3-Kinases | |
dc.subject | Response Evaluation Criteria in Solid Tumors | |
dc.subject | Biomarkers, Tumor | |
dc.title | Gefitinib and EGFR Gene Copy Number Aberrations in Esophageal Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-06-18 | |
rioxxterms.versionofrecord | 10.1200/jco.2016.70.3934 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | |
pubs.issue | 20 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Ashworth Collaborators | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Ashworth Collaborators | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 35 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Ashworth Collaborators | |
dc.contributor.icrauthor | Chong, Yu-Shing | |