1. Prognostic value of KRAS genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease
- Author
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Aude Lamy, Enrico Ricevuto, Mario Tosi, Thierry Frebourg, Antonella Dal Mas, Gino Coletti, Giancarlo Troncone, Katia Cannita, Corrado Ficorella, Daniela Di Giacomo, J.C. Sabourin, Gemma Bruera, Medical Oncology, Università degli Studi dell'Aquila (UNIVAQ)-S. Salvatore Hospital, Department of Experimental Medicine, Università degli Studi dell'Aquila (UNIVAQ), laboratoire de Génétique Somatique des Tumeurs, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Department of Biomorphologic and Functional Sciences, Università degli studi di Napoli Federico II, Pathology Department, S. Salvatore Hospital, Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), BMC, Ed., Università degli Studi dell'Aquila = University of L'Aquila (UNIVAQ)-S. Salvatore Hospital, Università degli Studi dell'Aquila = University of L'Aquila (UNIVAQ), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, University of Naples Federico II = Università degli studi di Napoli Federico II, Bruera, G, Cannita, K, Di Giacomo, D, Lamy, A, Troncone, Giancarlo, Dal Mas, A, Coletti, G, Frebourg, T, Sabourin, Jc, Tosi, M, Ficorella, C, and Ricevuto, E.
- Subjects
Oncology ,Male ,Colorectal cancer ,triplet chemotherapy plus bevacizumab ,lcsh:Medicine ,Disease ,medicine.disease_cause ,0302 clinical medicine ,Genotype ,KRAS mutations ,Infusions, Intravenous ,Medicine(all) ,0303 health sciences ,metastatic colorectal cancer ,General Medicine ,Middle Aged ,Prognosis ,intensive regimen ,3. Good health ,Bevacizumab ,Treatment Outcome ,030220 oncology & carcinogenesis ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Drug Therapy, Combination ,Female ,KRAS ,Colorectal Neoplasms ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Internal medicine ,Proto-Oncogene Proteins ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,medicine ,Humans ,neoplasms ,030304 developmental biology ,Aged ,business.industry ,lcsh:R ,medicine.disease ,digestive system diseases ,Oxaliplatin ,Irinotecan ,Regimen ,disease extension ,ras Proteins ,business - Abstract
Background Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of metastatic colorectal cancer (MCRC), particularly integrated with secondary liver surgery in liver-limited (L-L) patients. The prognostic value of the KRAS genotype in L-L and other or multiple metastatic (O/MM) MCRC patients treated with the FIr-B/FOx regimen was retrospectively evaluated. Methods Tumoral and metastatic samples were screened for KRAS codon 12 and 13 and BRAF mutations by SNaPshot and/or direct sequencing. Fit MCRC patients 2, days 1, 2, 8, 9, 15, 16, 22 and 23; irinotecan (CPT-11) 160 mg/m2 plus BEV 5 mg/kg, days 1, 15; oxaliplatin (OXP) 80 mg/m2, days 8, 22; every 4 weeks. MCRC patients were classified as L-L and O/MM. Activity and efficacy were evaluated and compared using log-rank test. Results In all, 59 patients were evaluated: 31 KRAS wild-type (53%), 28 KRAS mutant (47%). At 21.5 months median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were, respectively: KRAS wild-type 90%, 14 months, 38 months; KRAS mutant 67%, 11 months, 20 months. PFS and OS were not significantly different. PFS and OS were significantly different in L-L compared to O/MM evaluable patients. In KRAS wild-type patients, clinical outcome of 12 L-L compared to 18 O/MM was significantly different: PFS 21 versus 12 months and OS 47 versus 28 months, respectively. In KRAS mutant patients, the clinical outcome of 13 L-L compared to 14 O/MM was not significantly different: PFS 11 months equivalently and OS 39 versus 19 months, respectively. Conclusions The KRAS genotype wild-type and mutant does not significantly affect different clinical outcomes for MCRC patients treated with the first-line FIr-B/FOx intensive regimen. KRAS wild-type patients with L-L disease may achieve a significantly prolonged clinical outcome due to integration with secondary liver surgery, with respect to KRAS mutant patients.
- Published
- 2012