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Your search keyword '"Frattini, M."' showing total 19 results
Start Over Author "Frattini, M." Publisher elsevier bv
19 results on '"Frattini, M."'

5. A Phase I Trial of Ipilimumab (IPI) in Patients (PTS) with Myelodysplastic Syndromes (MDS) after Hypomethylating Agent (HMAS) Failure

Author

Zeidan, A., primary, Knaus, H., additional, Robinson, T., additional, Zeidner, J., additional, Blackford, A., additional, Duffield, A., additional, Rizzieri, D., additional, Frattini, M., additional, Levy, M.Y., additional, Schroeder, M., additional, Ferguson, A., additional, Sheldon, K., additional, Dezern, A., additional, Gojo, I., additional, Gore, S., additional, Streicher, H., additional, Luznik, L., additional, and Smith, B.D., additional

Published
2017
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15. P.197 Impact du génotypage de KRAS sur la réponse, la survie sans progression et la survie globale des patients réfractaires à l’irinotécan et traités par cetuximab plus irinotécan pour un cancer colorectal métastatique

Author

Di Fiore, F., primary, Van Cutsem, E., additional, Laurent-Puig, P., additional, Michel, P., additional, Siena, S., additional, Frattini, M., additional, de Roock, W., additional, Lievre, A., additional, and Sabine, T., additional

Published
2009
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16. PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients

Author

Perrone, F., primary, Lampis, A., additional, Orsenigo, M., additional, Di Bartolomeo, M., additional, Gevorgyan, A., additional, Losa, M., additional, Frattini, M., additional, Riva, C., additional, Andreola, S., additional, Bajetta, E., additional, Bertario, L., additional, Leo, E., additional, Pierotti, M.A., additional, and Pilotti, S., additional

Published
2009
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19. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis

Author

Philippe Rougier, George Fountzilas, Teresa Macarulla, Alice Gangloff, Sabine Tejpar, Bart Claes, Bruno Vincenzi, Vassiliki Kotoula, Giuseppe Tonini, Salvatore Siena, Frédéric Di Fiore, Mauro Delorenzi, Eric Van Cutsem, Alberto Bardelli, Federico Cappuzzo, Daniele Santini, Hubert Piessevaux, Sara De Dosso, Tine Plato Hansen, Konstantine T. Kalogeras, Milo Frattini, Miriam Martini, Diether Lambrechts, Josep Tabernero, Jef De Schutter, Francesca Molinari, Bart Biesmans, Camilla Qvortrup, Frédérique Penault-Llorca, Piercarlo Saletti, Fortunato Ciardiello, Andrea Sartore-Bianchi, David Bernasconi, Per Pfeiffer, Demetris Papamichael, Wendy De Roock, Pierre Laurent-Puig, DE ROOCK, W, Claes, B, Bernasconi, D, DE SCHUTTER, J, Biesmans, B, Fountzilas, G, Kalogeras, Kt, Kotoula, V, Papamichael, D, LAURENT PUIG, P, PENAULT LLORCA, F, Rougier, P, Vincenzi, B, Santini, D, Tonini, G, Cappuzzo, F, Frattini, M, Molinari, F, Saletti, P, DE DOSSO, S, Martini, M, Bardelli, A, Siena, S, SARTORE BIANCHI, A, Tabernero, J, Macarulla, T, DI FIORE, F, Gangloff, Ao, Ciardiello, Fortunato, Pfeiffer, P, Qvortrup, C, Hansen, Tp, VAN CUTSEM, E, Piessevaux, H, Lambrechts, D, Delorenzi, M, and Tejpar, S.

Subjects
Male, Neuroblastoma RAS viral oncogene homolog, Oncology, Pathology, Colorectal cancer, Cetuximab, medicine.disease_cause, Phosphatidylinositol 3-Kinases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Mutation frequency, Aged, 80 and over, education.field_of_study, Antibodies, Monoclonal, Middle Aged, Tumor Markers, Biological, Female, KRAS, Colorectal Neoplasms, medicine.drug, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, Population, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Internal medicine, Biomarkers, Tumor, Humans, Panitumumab, education, neoplasms, Survival analysis, Aged, Proportional Hazards Models, Retrospective Studies, business.industry, medicine.disease, Survival Analysis, digestive system diseases, Genes, ras, ROC Curve, Drug Resistance, Neoplasm, Multivariate Analysis, Mutation, business
Abstract

Following the discovery that mutant KRAS is associated with resistance to anti-epidermal growth factor receptor (EGFR) antibodies, the tumours of patients with metastatic colorectal cancer are now profiled for seven KRAS mutations before receiving cetuximab or panitumumab. However, most patients with KRAS wild-type tumours still do not respond. We studied the effect of other downstream mutations on the efficacy of cetuximab in, to our knowledge, the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre-KRAS selection era.1022 tumour DNA samples (73 from fresh-frozen and 949 from formalin-fixed, paraffin-embedded tissue) from patients treated with cetuximab between 2001 and 2008 were gathered from 11 centres in seven European countries. 773 primary tumour samples had sufficient quality DNA and were included in mutation frequency analyses; mass spectrometry genotyping of tumour samples for KRAS, BRAF, NRAS, and PIK3CA was done centrally. We analysed objective response, progression-free survival (PFS), and overall survival in molecularly defined subgroups of the 649 chemotherapy-refractory patients treated with cetuximab plus chemotherapy.40.0% (299/747) of the tumours harboured a KRAS mutation, 14.5% (108/743) harboured a PIK3CA mutation (of which 68.5% [74/108] were located in exon 9 and 20.4% [22/108] in exon 20), 4.7% (36/761) harboured a BRAF mutation, and 2.6% (17/644) harboured an NRAS mutation. KRAS mutants did not derive benefit compared with wild types, with a response rate of 6.7% (17/253) versus 35.8% (126/352; odds ratio [OR] 0.13, 95% CI 0.07-0.22; p0.0001), a median PFS of 12 weeks versus 24 weeks (hazard ratio [HR] 1.98, 1.66-2.36; p0.0001), and a median overall survival of 32 weeks versus 50 weeks (1.75, 1.47-2.09; p0.0001). In KRAS wild types, carriers of BRAF and NRAS mutations had a significantly lower response rate than did BRAF and NRAS wild types, with a response rate of 8.3% (2/24) in carriers of BRAF mutations versus 38.0% in BRAF wild types (124/326; OR 0.15, 95% CI 0.02-0.51; p=0.0012); and 7.7% (1/13) in carriers of NRAS mutations versus 38.1% in NRAS wild types (110/289; OR 0.14, 0.007-0.70; p=0.013). PIK3CA exon 9 mutations had no effect, whereas exon 20 mutations were associated with a worse outcome compared with wild types, with a response rate of 0.0% (0/9) versus 36.8% (121/329; OR 0.00, 0.00-0.89; p=0.029), a median PFS of 11.5 weeks versus 24 weeks (HR 2.52, 1.33-4.78; p=0.013), and a median overall survival of 34 weeks versus 51 weeks (3.29, 1.60-6.74; p=0.0057). Multivariate analysis and conditional inference trees confirmed that, if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA exon 20 mutations (in that order) gives additional information about outcome. Objective response rates in our series were 24.4% in the unselected population, 36.3% in the KRAS wild-type selected population, and 41.2% in the KRAS, BRAF, NRAS, and PIK3CA exon 20 wild-type population.While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.Belgian Federation against Cancer (Stichting tegen Kanker).

Published
2010

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