TY - JOUR
T1 - 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
T2 - the MOMA trial
AU - Cremolini, Chiara
AU - Marmorino, Federica
AU - Bergamo, Francesca
AU - Aprile, Giuseppe
AU - Salvatore, Lisa
AU - Masi, Gianluca
AU - Dell'Aquila, Emanuela
AU - Antoniotti, Carlotta
AU - Murgioni, Sabina
AU - Allegrini, Giacomo
AU - Borelli, Beatrice
AU - Gemma, Donatello
AU - Casagrande, Mariaelena
AU - Granetto, Cristina
AU - Delfanti, Sara
AU - Di Donato, Samantha
AU - Schirripa, Marta
AU - Sensi, Elisa
AU - Tonini, Giuseppe
AU - Lonardi, Sara
AU - Fontanini, Gabriella
AU - Boni, Luca
AU - Falcone, Alfredo
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - FOLFOXIRI plus bevacizumab
KW - Maintenance
KW - Metastatic colorectal cancer
KW - Metronomic chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=85060974360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060974360&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2018.12.028
DO - 10.1016/j.ejca.2018.12.028
M3 - Article
AN - SCOPUS:85060974360
VL - 109
SP - 175
EP - 182
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -