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Eur J Cancer. 2019 Mar;109:175-182. doi: 10.1016/j.ejca.2018.12.028. Epub 2019 Feb 5.

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.

Author information

1
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
2
Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology - IRCCS, Padova, Italy.
3
Department of Oncology, University and General Hospital, Udine, Italy; Department of Oncology, General Hospital, ULSS8 Berica - East District, 36100, Vicenza, Italy.
4
U.O.C Oncologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Roma, Italy.
5
Department of Medical Oncology, University Campus Biomedico, Rome, Italy.
6
Unit of Medical Oncology, Livorno Hospital, Department of Medical Oncology, Azienda Toscana Nord Ovest, Livorno, Italy.
7
Department of Medical Oncology, Hospital of Frosinone, Frosinone, Italy.
8
Department of Oncology, University and General Hospital, Udine, Italy.
9
Department of Oncology, S. Croce and Carle Teaching Hospital, Cuneo, Italy.
10
Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
11
Medical Oncology Department, Nuovo Ospedale-Santo Stefano, Prato, Italy.
12
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology - IRCCS, Padova, Italy.
13
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.
14
Clinical Trials Coordinating Center, Toscano Cancer Institute, University Hospital Careggi, Florence, Italy.
15
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. Electronic address: alfredo.falcone@med.unipi.it.

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.

KEYWORDS:

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

PMID:
30735919
DOI:
10.1016/j.ejca.2018.12.028

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