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https://dspace.uzhnu.edu.ua/jspui/handle/lib/10465
Название: | Analysis of KRAS/NRAS Mutations in a Phase 3 Study of Panitumumab With FOLFIRI Compared With FOLFIRI Alone as Second-Line Treatment for Metastatic Colorectal Cancer |
Авторы: | Marc Peeters Kelly S. Oliner Timothy Jay Price Andres Cervantes Alberto F. Sobrero Michel Ducreux Yevhen Hotko Thierry Andre Emily Chan Florian Lordick Cornelis J. A. Punt Andrew Strickland Gregory Wilson Tudor-Eliade Ciuleanu Laslo Roman Eric Van Cutsem Ying Tian Andre Scott Jung Roger Sidhu Scott D. Patterson |
Ключевые слова: | Gastrointestinal cancers: colorectal; Phase I-III Trials_Gastrointestinal cancers: colorectal |
Дата публикации: | 2015 |
Краткий осмотр (реферат): | 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. |
Тип: | Text |
Тип публикации: | Стаття |
URI (Унифицированный идентификатор ресурса): | https://dspace.uzhnu.edu.ua/jspui/handle/lib/10465 |
Располагается в коллекциях: | Наукові публікації кафедри радіології та онкології |
Файлы этого ресурса:
Файл | Описание | Размер | Формат | |
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1078-0432.CCR-15-0526.full.pdf | 620.62 kB | Adobe PDF | Просмотреть/Открыть |
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