Phase III Trial of Cetuximab, Bevacizumab, and 5-Fluorouracil/Leucovorin vs. FOLFOX-Bevacizumab in Colorectal Cancer

详细信息	查看全文 | 推荐本文 |

• 作者：Leonard Saltz¹ ; ^{saltzl@mskcc.org} ; Suprith Badarinath² ; Shaker Dakhil³ ; Bryan Bienvenu⁴ ; W. Graydon Harker⁵ ; George Birchfield⁶ ; ⁷ ; Laurence K. Tokaz⁶ ; ⁸ ; David Barrera⁶ ; ⁹ ; Paul R. Conkling⁶ ; ¹⁰ ; Mark A. O'Rourke⁶ ; ¹¹ ; Donald A. Richards⁶ ; ¹² ; Diane Reidy¹ ; David Solit¹ ; Efsevia Vakiani¹ ; Marinella Capanu¹ ; Amy Scales⁶ ; Feng Zhan⁶ ; Kristi A. Boehm⁶ ; Lina Asmar⁶ ; Allen Cohn⁶ ; ¹³
• 关键词：Colorectal cancer ; cetuximab ; KRAS ; oxaliplatin
• 刊名：Clinical Colorectal Cancer
• 出版年：2012
• 期刊代码：pca91_15330028
• 类别：med
• 出版时间：June, 2012
• 卷：11
• 期：2
• 页码：101-111
• 文件大小：512 K

摘要

Background

Cetuximab (C), alone or with irinotecan, demonstrates activity in irinotecan-refractory colorectal cancer (CRC). Activity of 5-fluorouracil (5-FU), leucovorin (L), and bevacizumab (B), and preliminary data of cetuximab + bevacizumab, and toxicity profiles suggests that FOLF-CB (5-FU, L, C+B) may have activity with a favorable toxicity profile as first-line therapy.

Methods

Eligible patients were randomized at registration to either arm A (mFOLFOX6-B) (modified, 5-FU. L (folinic acid), oxaliplatin (O) + bevacizumab), administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg, oxaliplatin 85 mg/m², leucovorin 400 mg/m², and 5-FU 400 mg/m² then 1200 mg/m²/day for 48 hours, or arm B (FOLF-CB), which included bevacizumab, leucovorin, and 5-FU as in arm A and cetuximab 400 mg/m² day 1 cycle 1; all other weekly cetuximab doses were 250 mg/m².

Results

Two hundred forty-seven patients (arm A/arm B 124/123) were enrolled, and 239 were treated (118/121). Twelve-month progression-free survival (PFS) was 45%/32%, objective response rates (ORR) (complete response [CR] + partial response [PR]) were 52%/41%, disease control rates (CR+PR+stable disease [SD]) were 87%/83%, and median overall survival (OS) was 21/19.5 months, respectively. Grade 3-4 neutropenia was higher in arm A (28%/7%), as was grade 3 fatigue (12%/3%), and grade 3 neuropathy (11%/< 1%), whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity, except in arm B patients with KRAS-mutated tumors, which resulted in inferior PFS. Patient satisfaction favored the control (mFOLFOX6-B).

Conclusion

FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR, and was not more acceptable to patients. This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC.