Sequential and Concurrent FOLFOXIRI/Bevacizumab Regimens Versus FOLFOX/Bevacizumab in First-Line Metastatic Colorectal Cancer

Summary

This randomized, open-label, multicenter study will evaluate the efficacy and safety of folinic acid (leucovorin), 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) / bevacizumab regimens (concurrent and sequential) versus folinic acid (leucovorin), 5-fluorouracil, and oxaliplatin (FOLFOX) / bevacizumab in first-line in participants with metastatic colorectal cancer. Participants will be randomized to receive bevacizumab 5 milligrams per kilogram (mg/kg) intravenously every 2 weeks with either concurrent or sequential FOLFOXIRI or with FOLFOX for 4 to 6 months of induction therapy, followed by maintenance therapy with bevacizumab plus either leucovorin/5-fluorouracil or capecitabine until disease progression occurs. After disease progression, participants will receive treatment with a fluoropyrimidine-based chemotherapy plus bevacizumab.

Timeline

Start

2013-01-23

Primary completion

2016-03-14

Completion

2016-03-14

Outcome

Mixed primary results

paper ORR between cFOLFOXIRI-BEV and FOLFOX-BEV did not significantly differ (p = .132); thus, the primary ORR endpoint was not met. PMID 30552157 ↗

paper Median PFS was higher with pooled concurrent and sequential FOLFOXIRI-BEV versus FOLFOX-BEV (11.7 vs. 9.5 months; hazard ratio, 0.7; 90% confidence interval, 0.5-0.9). PMID 30552157 ↗

registry Arm C: FOLFOX + Bevacizumab vs Arms A + B: Pooled FOLFOXIRI + Bevacizumab; p = 0.005; Hazard Ratio (HR) 0.68 (90% CI 0.53 to 0.88) NCT01765582 ↗

Publications

• Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
• Hurwitz HI, Tan BR, Reeves JA, Xiong H, Somer B, Lenz HJ, Hochster HS, Scappaticci F, Palma JF, Price R, Lee JJ, Nicholas A, Sommer N, Bendell J. Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Irinotecan	Small molecule	165 mg/m2	Intravenous
Subject	Irinotecan	Small molecule	180 mg/m2	Intravenous
Subject	Leucovorin	Small molecule	200 mg/m2	Intravenous
Subject	Leucovorin	Small molecule	400 mg/m2	Intravenous
Subject	fluorouracil	Small molecule	400 mg/m2	Intravenous
Subject	fluorouracil	Small molecule	2400 mg/m2	Intravenous
Subject	fluorouracil	Small molecule	3200 mg/m2	Intravenous
Background	Bevacizumab	Monoclonal antibody	2.5 mg/kg	Intravenous
Background	Bevacizumab	Monoclonal antibody	5 mg/kg	Intravenous
Background	Bevacizumab	Monoclonal antibody	7.5 mg/kg	Intravenous
Background	Capecitabine	Small molecule	850 mg/kg	Oral
Background	Capecitabine	Small molecule	1000 mg/kg	Oral
Background	Oxaliplatin	Small molecule	85 mg/m2	Intravenous

Indications