Biweekly Cetuximab Plus FOLFOX6 as First-Line Therapy in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The CEBIFOX Trial

被引：7

作者：

Kasper, Stefan ^{[5
,6
]}

Meiler, Johannes ^{[1
,5
]}

Knipp, Heike ^{[2
,7
]}

Hohler, Thomas ^{[8
]}

Reimer, Peter ^{[9
]}

Steinmetz, Tilman ^{[10
]}

Berger, Winfried ^{[11
]}

Linden, Gabriele ^{[5
]}

Reis, Henning ^{[12
]}

Markus, Peter ^{[13
]}

Paul, Andreas ^{[6
,14
]}

Dechene, Alexander ^{[3
,15
]}

Schumacher, Brigitte ^{[16
]}

Kostbade, Karina ^{[5
]}

Virchow, Isabel ^{[5
]}

Ting, Saskia ^{[12
]}

Worm, Karl ^{[12
]}

Schmid, Kurt W. ^{[6
,12
]}

Herold, Thomas ^{[12
]}

Wiesweg, Marcel ^{[5
]}

Schuler, Martin ^{[5
,6
]}

Trarbach, Tanja ^{[4
,5
]}

机构：

[1] Dr Hancken Hosp, Ambulatory Hlth Care Ctr Hematol & Med Oncol, Stade, Germany

[2] Gen Hosp Herdecke, Ambulatory Hlth Care Ctr Hematol & Med Oncol, Herdecke, Germany

[3] Univ Hosp Nurnberg, Dept Gastroenterol & Hepatol, Nurnberg, Germany

[4] Wilhelmshaven Hosp, Ctr Tumour Biol & Integrat Med, Wilhelmshaven, Germany

[5] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany

[6] German Canc Consortium DKTK, Heidelberg, Germany

[7] Alfried Krupp von Bohlen & Halbach Hosp, Dept Med 1, Essen, Germany

[8] Prosper Hosp, Dept Med 1, Recklinghausen, Germany

[9] Protestant Hosp, Dept Hematol & Med Oncol, Essen, Germany

[10] Grp Practice Hematol Oncol, Cologne, Germany

[11] Catholic Hosp, Dept Hematol & Med Oncol, Essen, Germany

[12] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Inst Pathol, Essen, Germany

[13] Elisabeth Hosp, Dept Gen Visceral & Trauma Surg, Essen, Germany

[14] Univ Duisburg Essen, Dept Gen Visceral & Transplantat Surg, West German Canc Ctr, Univ Hosp Essen, Essen, Germany

[15] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Gastroenterol & Hepatol, Essen, Germany

[16] Elisabeth Hosp, Dept Gastroenterol, Essen, Germany

来源：

CLINICAL COLORECTAL CANCER | 2020年 / 19卷 / 04期

关键词：

Biweekly cetuximab; BRAF mutation; Metastatic colorectal cancer; Primary tumor localization; RAS mutation; EVERY 2ND WEEK; PHASE-II; LEUCOVORIN; MUTATIONS; FLUOROURACIL; CHEMOTHERAPY; OXALIPLATIN; BEVACIZUMAB; FOLFIRI; BRAF;

D O I：

10.1016/j.clcc.2020.03.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The CEBIFOX study evaluated the efficacy of biweekly cetuximab/FOLFOX6 regimen in RAS wild-type metastatic colorectal cancer (mCRC). Fifty-seven patients were included in the intention-to-treat analyses. The objective response rate in the all RAS wild-type population was 70.3% with a median progression-free and overall survival of 10.9 and 33.8 months. This study supports the efficacy and safety of biweekly cetuximab/FOLFOX6 in RAS wild-type mCRC. Background: The multicenter, single-arm, phase II study CEBIFOX evaluated the efficacy of a biweekly cetuximab administration in combination with FOLFOX6 as first-line therapy in KRAS (exon 2) wild-type (wt) metastatic colorectal cancer (mCRC). Patients and methods: Patients received FOLFOX6 with cetuximab (500 mg/m(2)) every second week. Primary endpoint was objective response rate (ORR), among others secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), and patient-reported outcome (PRO). The impact on the treatment efficacy was evaluated in explorative subgroup analyses, including extended molecular profiling and primary tumor location. Results: In total, 57 were included in the intention-to-treat (ITT) analyses. New RAS mutations were detected in 14.0% by post hoc next-generation sequencing analysis in 43 patients. The ORR in the all RASwt population was 70.3% with a median PFS and OS of 10.9 (95% confidence interval [CI], 9.0-12.9) and 33.8 (95% CI, 21.1-45.5) months. Grade 3-5 adverse events occurred in 66.7% of the ITT, without significant impact on the PRO. Patients with right-sided primary tumors had a reduced ORR (54.5%), and median PFS and OS (10.1 and 23.8 months). BRAF mutations were detected in 11.3%. These patients had a significantly lower ORR, and median PFS and OS. Patients with RASwt/BRAFwt tumors had a notably high median PFS and OS of 14.3 and 38.9 months. Conclusions: This study supports the efficacy and safety of biweekly cetuximab given in combination with FOLFOX6 in patients with RASwt/BRAFwt mCRC with left-sided primary tumor. CEBIFOX is the first trial reporting the complete dataset, including extended molecular profiling and tumor location of a biweekly administered cetuximab/FOLFOX6 in mCRC. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：236 / +

页数：18

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