Abstract
BackgroundFOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression.MethodsWe performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction.ResultsLonger 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045).ConclusionsFirst-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.
Highlights
FOLFOXIRI/bevacizumab is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer
The Phase 3 TRIBE2 (NCT02339116) trial confirmed the superiority of the upfront exposure to FOLFOXIRI/bev followed by the reintroduction of the same regimen after first disease progression, as compared with the pre-planned sequential administration of the three cytotoxics across two subsequent lines of therapy (FOLFOX (5fluorouracil, L-leucovorin and oxaliplatin)/bev followed by FOLFIRI
In the TRIBE2 study, patients were randomised in a 1:1 ratio to FOLFOX/bev followed by FOLFIRI/ bev after disease progression or FOLFOXIRI/bev followed by the reintroduction of the same agents after disease progression; all treatments were administrated up to eight cycles followed by 5fluorouracil plus bev maintenance until disease progression, unacceptable adverse events or consent withdrawal.[8]
Summary
FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. FOLFOXIRI (5-fluorouracil, L-leucovorin, oxaliplatin and irinotecan)/ bevacizumab (bev) is regarded by main guidelines as an efficacious first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC),[1,2] according to the results of several randomised trials.[3,4,5,6,7]. The Phase 3 TRIBE2 (NCT02339116) trial confirmed the superiority of the upfront exposure to FOLFOXIRI/bev followed by the reintroduction of the same regimen after first disease progression, as compared with the pre-planned sequential administration of the three cytotoxics across two subsequent lines of therapy (FOLFOX (5fluorouracil, L-leucovorin and oxaliplatin)/bev followed by FOLFIRI TRIBE trial that compared FOLFOXIRI/bev with FOLFIRI/bev as upfront treatment, where the choice of the treatment after progression was left at investigator’s choice, further therapy was administered to the majority of patients progressed after first line (80%).[3]
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