Highlights
- •The addition of metronomic chemotherapy to bevacizumab (bev) during maintenance does not significantly improve PFS.
- •5FU/bev is the standard maintenance following upfront FOLFOXIRI/bev.
- •The activity of FOLFOXIRI/bev is confirmed with 4 instead of 6 months duration.
- •Results among BRAF mutants are consistent with previous findings with FOLFOXIRI/bev.
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
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Article info
Publication history
Published online: February 05, 2019
Accepted:
December 30,
2018
Received in revised form:
December 21,
2018
Received:
October 6,
2018
Identification
Copyright
© 2019 Elsevier Ltd. All rights reserved.
