Phase II randomised study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial

Chiara Cremolini, Federica Marmorino, Francesca Bergamo, Giuseppe Aprile, Lisa Salvatore, Gianluca Masi, Emanuela Dell'Aquila, Carlotta Antoniotti, Sabina Murgioni, Giacomo Allegrini, Beatrice Borelli, Donatello Gemma, Mariaelena Casagrande, Cristina Granetto, Sara Delfanti, Samantha Di Donato, Marta Schirripa, Elisa Sensi, Giuseppe Tonini, Sara LonardiGabriella Fontanini, Luca Boni, Alfredo Falcone

Research output: Contribution to journalArticle

Abstract

Background: Alternating induction and maintenance phases is a common strategy in metastatic colorectal cancer (mCRC). Metronomic chemotherapy (metroCT) may represent a well-tolerated chemotherapy backbone for maximising bevacizumab effect during maintenance. The MOMA trial was designed to compare metroCT plus bevacizumab versus bevacizumab alone as maintenance following 4 months of induction with FOLFOXIRI plus bevacizumab. Patients and methods: In this phase II study, patients with unresectable mCRC were randomised to receive up to 8 cycles of FOLFOXIRI plus bevacizumab, followed by bevacizumab (arm A) or the same regimen followed by bevacizumab plus metroCT (capecitabine 500 mg/three times per day and cyclophosphamide 50 mg/die, arm B) until disease progression. The primary end-point was progression-free survival (PFS). According to the Rubinstein and Korn's design, to detect a hazard ratio[HR] of 0.75 favouring arm B, with 1 sided-alpha and beta errors of 15% and 80%, 173 events and 222 patients were required. Results: Between May 2012 and March 2015, 232 patients, mostly with RAS (65%) or BRAF (9%) mutant tumours, were randomised in 16 Italian centres. At a median follow-up of 47.8 months, 210 and 164 progression and death events were registered. The primary end-point was not met. Median PFS was 10.3 and 9.4 months in arm B and A, respectively (HR: 0.94 [70% confidence interval {CI}: 0.82–1.09], p = 0.680). No significant differences were reported in terms of overall survival (OS) (median OS arm B/A: 22.5/28 months; HR: 1.16 [95%CI: 0.99–1.37], p = 0.336). Response rate with FOLFOXIRI plus bevacizumab was 63% (arm B/A: 58%/68%). In the liver-limited subgroup, the secondary resection rate was 49% (arm B/A: 45%/55%). Conclusions: The addition of metroCT to maintenance with bevacizumab does not significantly improve PFS of mCRC patients. The activity of FOLFOXIRI plus bevacizumab is confirmed in a population with high prevalence of RAS/BRAF mutations treated with a 4-months induction. Trial registration: www.clinicaltrials.gov NCT02271464.

Original languageEnglish
Pages (from-to)175-182
Number of pages8
JournalEuropean Journal of Cancer
Volume109
DOIs
Publication statusPublished - Mar 1 2019

Keywords

  • FOLFOXIRI plus bevacizumab
  • Maintenance
  • Metastatic colorectal cancer
  • Metronomic chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase II randomised study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial'. Together they form a unique fingerprint.

  • Cite this