Gefitinib and EGFR Gene Copy Number Aberrations in Esophageal Cancer
| العنوان: | Gefitinib and EGFR Gene Copy Number Aberrations in Esophageal Cancer |
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| المؤلفون: | Stephen Falk, Susan J Dutton, Wasat Mansoor, David A J Stevenson, Caroline Clark, Russell D. Petty, Aileen Osborne, Asa Dahle-Smith, Angel Garcia-Alonso, Mark Harrison, Joyce Thompson, Graeme I. Murray, Ian Chau, Irene Chong, Jonathan Wadsley, Corran Roberts, Doreen Massie, Zosia Miedzybrodzka, Anirban Chatterjee, Sean Elyan, David Walter Fyfe, David Ferry |
| المصدر: | Journal of Clinical Oncology. 35:2279-2287 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Cancer Research, Esophageal Neoplasms, DNA Mutational Analysis, Gene Dosage, medicine.disease_cause, Tyrosine-kinase inhibitor, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Medicine, Single-Blind Method, Epidermal growth factor receptor, In Situ Hybridization, Fluorescence, Randomized Controlled Trials as Topic, biology, Gefitinib, Middle Aged, Esophageal cancer, ErbB Receptors, Survival Rate, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Female, KRAS, Signal Transduction, medicine.drug, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, medicine.drug_class, Antineoplastic Agents, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, Humans, neoplasms, Survival rate, Aged, business.industry, Gene Amplification, Cancer, Genes, erbB-1, medicine.disease, respiratory tract diseases, 030104 developmental biology, Clinical Trials, Phase III as Topic, Mutation, Quinazolines, biology.protein, business |
| الوصف: | 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. |
| تدمد: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2016.70.3934 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8371b4cd78ae0dea0b7758a0d5bded2b https://doi.org/10.1200/jco.2016.70.3934 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8371b4cd78ae0dea0b7758a0d5bded2b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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| DOI: | 10.1200/jco.2016.70.3934 |