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

Autor: 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, Abraham, C, Chesnay, L, Amant, F, Anderson, R, Azzedine, A, Benedetto, Chiara, Bertelli, G, Berteloot, P, Berton Rigaud, D, Biglia, N, Bonichon Lamichhane, N, Bougnoux, P, Bourbouloux, E, Bourcier, C, Buck, M, Campone, M, Canuto, Em, Casado Herraez, A, Cauvin, I, Chauvenet, L, Chevalier Place, A, Cottu, P., Cretin, J, Cumin, I, Curé, H, Dalenc, F, Danese, S, Davis, A, Debruyne, P, Delplanque, G, Delva, R, D'Hondt, V, Dramais, D, Durando, X, El Kouri, C, Esteban, C, Fabbro, M, Falandry, C, Filleul, B, Floquet, A, Fumoleau, P, Garcia Varella, M, Garnier, C, Gilby, E, Gladieff, L, Goffin, F, Gouttebel, M., Green, Ja, Guastalla, J., Hardy Bessard, A., Hirsch, F, Hughes, A, Jaubert, D, Kaminsky, M., Katsaros, D, Largillier, R, Lebrun Jezekova, D, Leduc, B, Leheurteur, M, Lesoin, A, Leunen, K, Levasseur, N, Leyronnas, C, Llory, J., Lortholary, A, Mayer, F, Mayeur, D, Mendiola, C, Mignot, L, Morgan, J, Mouret Reynier, M., Neven, P, Petit, T, Picardo, E, Plaza, J, Pluvio Coronado, M, Priou, F, Pujade Lauraine, E, Coquard, I, Reed, N, Rigault de la Longrais, I, Scholl, S, Sillet Bach, I, Steer, C, Summers, J, Trillet Lenoir, V, Van Dam, P, Van Der Burg ME, Vanlerenberghe, E, Vannetzel, J., Vergote, I, Aragon, Ja, Waters, J, Weber, B, Yazbek, G, Zola, P.
Přispěvatelé: Medical Oncology, Other departments
Rok vydání: 2015
Předmět:
Neuroblastoma RAS viral oncogene homolog
Oncology
Adult
Cancer Research
medicine.medical_specialty
Organoplatinum Compounds
medicine.disease_cause
Article
Aged
Aged
80 and over
Antineoplastic Combined Chemotherapy Protocols
Biomarkers
Tumor
Disease Progression
Disease-Free Survival
Erlotinib Hydrochloride
Female
Humans
Middle Aged
Mutation
Ovarian Neoplasms
Protein Kinase Inhibitors
Protein Kinases
Receptor
Epidermal Growth Factor
Pharmacology (medical)
SDG 3 - Good Health and Well-being
Internal medicine
80 and over
Medicine
EGFR Gene Amplification
Epidermal growth factor receptor
neoplasms
Tumor
Epidermal Growth Factor
biology
business.industry
Cancer
medicine.disease
ErbB Receptors
biology.protein
Biomarker (medicine)
Erlotinib
KRAS
business
Ovarian cancer
Biomarkers
Receptor
medicine.drug
Zdroj: Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Targeted Oncology, 10(4), 583-596. Springer Paris
Targeted oncology, 10(4), 583-596. Springer Paris
ISSN: 1776-2596
1776-260X
Popis: 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. 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). 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. 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.
Databáze: OpenAIRE
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