Phase III trial of cetuximab, bevacizumab, and 5-fluorouracil/leucovorin vs. FOLFOX-bevacizumab in colorectal cancer. Academic Article uri icon

Overview

abstract

  • 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/m(2), leucovorin 400 mg/m(2), and 5-FU 400 mg/m(2) then 1200 mg/m(2)/day for 48 hours, or arm B (FOLF-CB), which included bevacizumab, leucovorin, and 5-FU as in arm A and cetuximab 400 mg/m(2) day 1 cycle 1; all other weekly cetuximab doses were 250 mg/m(2). 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.

authors

  • Saltz, Leonard B.
  • Badarinath, Suprith
  • Dakhil, Shaker
  • Bienvenu, Bryan
  • Harker, W Graydon
  • Birchfield, George
  • Tokaz, Laurence K
  • Barrera, David
  • Conkling, Paul R
  • O'Rourke, Mark A
  • Richards, Donald A
  • Reidy, Diane
  • Solit, David
  • Vakiani, Efsevia
  • Capanu, Marinella
  • Scales, Amy
  • Zhan, Feng
  • Boehm, Kristi A
  • Asmar, Lina
  • Cohn, Allen

publication date

  • November 4, 2011

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Colorectal Neoplasms

Identity

Scopus Document Identifier

  • 84860785653

Digital Object Identifier (DOI)

  • 10.1016/j.clcc.2011.05.006

PubMed ID

  • 22055112

Additional Document Info

volume

  • 11

issue

  • 2