دورية أكاديمية
Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer.
| العنوان: | Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer. |
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| المؤلفون: | Peeters M; Antwerp University Hospital and University of Antwerp, Edegem, Belgium. Marc.Peeters@uza.be., Oliner KS; Amgen Inc., Thousand Oaks, California, USA., Price TJ; Queen Elizabeth Hospital and University of Adelaide, Woodville, Australia., Cervantes A; Biomedical Research Institute INCLIVA, University of Valencia, Spain., Sobrero AF; Ospedale San Martino, Genova, Italy., Ducreux M; Institut Gustave Roussy, Villejuif, and Paris-Sud University, Le Kremlin Bicêtre, Paris, France., Hotko Y; Uzhgorod National University, Uzhgorod, Ukraine., André T; Hôpital Saint Antoine and Université Pierre et Marie Curie (UMPC; Paris VI), Paris, France., Chan E; Vanderbilt University Medical Center, Nashville, Tennessee, USA., Lordick F; University Cancer Center, Leipzig, Germany., Punt CJ; Academic Medical Center, Amsterdam, the Netherlands., Strickland AH; Monash Medical Center, East Bentleigh, Australia., Wilson G; Christie Hospital, Manchester, United Kingdom., Ciuleanu TE; Institutul Oncologic Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca, Romania., Roman L; Leningrad Regional Oncology Dispensary, Saint Petersburg, Russia., Van Cutsem E; University Hospitals and KU Leuven, Leuven, Belgium., He P; Amgen Inc., Thousand Oaks, California, USA., Yu H; Amgen Inc., Thousand Oaks, California, USA., Koukakis R; Amgen (Europe) GmbH, Zug, Switzerland., Terwey JH; Amgen (Europe) GmbH, Zug, Switzerland., Jung AS; Amgen Inc., Thousand Oaks, California, USA., Sidhu R; Amgen Inc., Thousand Oaks, California, USA., Patterson SD; Amgen Inc., Thousand Oaks, California, USA. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2015 Dec 15; Vol. 21 (24), pp. 5469-79. Date of Electronic Publication: 2015 Sep 04. |
| نوع المنشور: | Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Genes, ras* , Mutation*, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Camptothecin/*analogs & derivatives , Colorectal Neoplasms/*drug therapy , Colorectal Neoplasms/*genetics, Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Camptothecin/adverse effects ; Camptothecin/therapeutic use ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; DNA Mutational Analysis ; Exons ; Female ; Fluorouracil/adverse effects ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/adverse effects ; Leucovorin/therapeutic use ; Male ; Middle Aged ; Neoplasm Metastasis ; Panitumumab ; Proportional Hazards Models ; Proto-Oncogene Proteins B-raf/genetics ; Retreatment ; Survival Analysis ; Treatment Outcome |
| مستخلص: | Purpose: We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective-retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Experimental Design: Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) were coprimary endpoints. Results: The RAS ascertainment rate was 85%; 18% of wild-type KRAS exon 2 tumors harbored other RAS mutations. For PFS and OS, the hazard ratio (HR) for panitumumab plus FOLFIRI versus FOLFIRI alone more strongly favored panitumumab in the wild-type RAS population than in the wild-type KRAS exon 2 population [PFS HR, 0.70 (95% confidence interval [CI], 0.54-0.91); P = 0.007 vs. 0.73 (95% CI, 0.59-0.90); P = 0.004; OS HR, 0.81 (95% CI, 0.63-1.03); P = 0.08 vs. 0.85 (95% CI, 0.70-1.04); P = 0.12]. Patients with RAS mutations were unlikely to benefit from panitumumab. Among RAS wild-type patients, the objective response rate was 41% in the panitumumab-FOLFIRI group versus 10% in the FOLFIRI group. Conclusions: Patients with RAS mutations were unlikely to benefit from panitumumab-FOLFIRI and the benefit-risk of panitumumab-FOLFIRI was improved in the wild-type RAS population compared with the wild-type KRAS exon 2 population. These findings support RAS testing for patients with mCRC. Clin Cancer Res; 21(24); 5469-79. ©2015 AACR.See related commentary by Salazar and Ciardiello, p. 5415. (©2015 American Association for Cancer Research.) |
| التعليقات: | Comment in: Clin Cancer Res. 2015 Dec 15;21(24):5415-6. (PMID: 26463710) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT00339183 |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 6A901E312A (Panitumumab) EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) Q573I9DVLP (Leucovorin) U3P01618RT (Fluorouracil) XT3Z54Z28A (Camptothecin) |
| SCR Protocol: | IFL protocol |
| تواريخ الأحداث: | Date Created: 20150906 Date Completed: 20160915 Latest Revision: 20220410 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1158/1078-0432.CCR-15-0526 |
| PMID: | 26341920 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-15-0526 |