دورية أكاديمية

Epidermal Growth Factor Receptor (EGFR) Pathway Biomarkers in the Randomized Phase III Trial of Erlotinib Versus Observation in Ovarian Cancer Patients with No Evidence of Disease Progression after First-Line Platinum-Based Chemotherapy.

التفاصيل البيبلوغرافية
العنوان: Epidermal Growth Factor Receptor (EGFR) Pathway Biomarkers in the Randomized Phase III Trial of Erlotinib Versus Observation in Ovarian Cancer Patients with No Evidence of Disease Progression after First-Line Platinum-Based Chemotherapy.
المؤلفون: Despierre, Evelyn, Vergote, Ignace, Anderson, Ryan, Coens, Corneel, Katsaros, Dionyssios, Hirsch, Fred R, Boeckx, Bram, Varella-Garcia, Marileila, Ferrero, Annamaria, Ray-Coquard, Isabelle, Berns, Els M J J, Casado, Antonio, Lambrechts, Diether, Jimeno, Antonio, European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG, Groupe d’Investigateurs Nationaux pour les Etudes des Cancers de l’Ovaire (GINECO, Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (A-AGO, National Cancer Research Institute (NCRI, Australia New Zealand Gynaecological Oncology Group (ANZGOG, Mario Negri Gynecologic Oncology group (MaNGO, Goffin, Frédéric
المصدر: Targeted Oncology, 10 (4), 583 - 596 (2015-12)
بيانات النشر: Springer-Verlag France, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Biomarkers, Tumor, Organoplatinum Compounds, Protein Kinase Inhibitors, Erlotinib Hydrochloride, Protein Kinases, EGFR protein, human, ErbB Receptors, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor/genetics, Biomarkers, Tumor/metabolism, Disease Progression, Disease-Free Survival, ErbB Receptors/genetics, ErbB Receptors/metabolism, Erlotinib Hydrochloride/therapeutic use, Female, Humans, Middle Aged, Mutation, Organoplatinum Compounds/administration & dosage, Ovarian Neoplasms/drug therapy, Ovarian Neoplasms/enzymology, Ovarian Neoplasms/genetics, Protein Kinase Inhibitors/therapeutic use, Protein Kinases/genetics, Protein Kinases/metabolism, Antineoplastic Combined Chemotherapy Protocols, Ovarian Neoplasms, Receptor, Epidermal Growth Factor, Oncology, Cancer Research, Pharmacology (medical), Human health sciences, Sciences de la santé humaine, Oncologie
الوصف: [en] BACKGROUND: In this work, we aimed to identify molecular epidermal growth factor receptor (EGFR) tissue biomarkers in patients with ovarian cancer who were treated within the phase III randomized European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG) 55041 study comparing erlotinib with observation in patients with no evidence of disease progression after first-line platinum-based chemotherapy.METHODS: Somatic mutations in KRAS, BRAF, NRAS, PIK3CA, EGFR, and PTEN were determined in 318 (38 %) and expression of EGFR, pAkt, pMAPK, E-cadherin and Vimentin, and EGFR and HER2 gene copy numbers in 218 (26 %) of a total of 835 randomized patients. Biomarker data were correlated with progression-free survival (PFS) and overall survival (OS).RESULTS: Only 28 mutations were observed among KRAS, BRAF, NRAS, PIK3CA, EGFR, and PTEN (in 7.5 % of patients), of which the most frequent were in KRAS and PIK3CA. EGFR mutations occurred in only three patients. When all mutations were pooled, patients with at least one mutation in KRAS, NRAS, BRAF, PIK3CA, or EGFR had longer PFS (33.1 versus 12.3 months; HR 0.57; 95 % CI 0.33 to 0.99; P = 0.042) compared to those with wild-type tumors. EGFR overexpression was detected in 93 of 218 patients (42.7 %), and 66 of 180 patients (36.7 %) had EGFR gene amplification or high levels of copy number gain. Fifty-eight of 128 patients had positive pMAPK expression (45.3 %), which was associated with inferior OS (38.9 versus 67.0 months; HR 1.81; 95 % CI 1.11 to 2.97; P = 0.016). Patients with positive EGFR fluorescence in situ hybridization (FISH) status had worse OS (46.1 months) than those with negative status (67.0 months; HR 1.56; 95 % CI 1.01 to 2.40; P = 0.044) and shorter PFS (9.6 versus 16.1 months; HR 1.57; 95 % CI 1.11 to 2.22; P = 0.010). None of the investigated biomarkers correlated with responsiveness to erlotinib.CONCLUSIONS: In this phase III study, increased EGFR gene copy number was associated with worse OS and PFS in patients with ovarian cancer. It remains to be determined whether this association is purely prognostic or is also predictive.
نوع الوثيقة: journal article
http://purl.org/coar/resource_type/c_6501
article
peer reviewed
اللغة: English
Relation: http://link.springer.com/content/pdf/10.1007/s11523-015-0369-6.pdf; urn:issn:1776-2596; urn:issn:1776-260X
DOI: 10.1007/s11523-015-0369-6
URL الوصول: https://orbi.uliege.be/handle/2268/309161
حقوق: open access
http://purl.org/coar/access_right/c_abf2
info:eu-repo/semantics/openAccess
رقم الأكسشن: edsorb.309161
قاعدة البيانات: ORBi
الوصف
DOI:10.1007/s11523-015-0369-6