Bevacizumab in Combination With Either FOLFOX-4 or XELOX-2 in First-line Treatment of Patients With Metastatic Colorectal Cancer: A Multicenter Randomized Phase II Trial of the Gruppo Oncologico dell'Italia Meridionale (GOIM 2802)

Clin Colorectal Cancer. 2020 Jun;19(2):109-115. doi: 10.1016/j.clcc.2020.01.003. Epub 2020 Jan 30.

Abstract

Introduction: Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC.

Materials and methods: Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed.

Results: Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5.

Conclusion: This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC.

Keywords: Capecitabine; Elderly; Fluoropyrimidine; Frail; Non-comparative.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Capecitabine / administration & dosage*
  • Capecitabine / adverse effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / diagnosis
  • Nausea / epidemiology
  • Neutropenia / chemically induced
  • Neutropenia / diagnosis
  • Neutropenia / epidemiology
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Oxaloacetates / administration & dosage*
  • Oxaloacetates / adverse effects
  • Progression-Free Survival
  • Severity of Illness Index

Substances

  • Organoplatinum Compounds
  • Oxaloacetates
  • Bevacizumab
  • Capecitabine
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol
  • XELOX

Associated data

  • EudraCT/2010-022091-31