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Bending the Curve Trial by Trial
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TRIBE2

FIRST-LINE FOLFOXIRI PLUS BEVACIZUMAB FOLLOWED BY REINTRODUCTION OF FOLFOXIRI PLUS BEVACIZUMAB AT PROGRESSION Versus FOLFOX PLUS BEVACIZUMAB FOLLOWED BY FOLFIRI PLUS BEVACIZUMAB AT PROGRESSION IN FIRST- AND SECOND-LINE TREATMENT OF UNRESECTABLE METASTATIC COLORECTAL CANCER.

Phase 3N = 679NCT02339116

Population
Previously untreated unresectable metastatic colorectal cancer, age 18 to 75 years
Design
Open-label, multicentre phase 3 trial in 58 Italian oncology units: patients aged 18 to 75 years with unresectable, previously untreated metastatic colorectal cancer were randomly assigned (1:1) to a preplanned strategy of first-line FOLFOXIRI plus bevacizumab with reintroduction of the same regimen after progression (experimental), or mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab after progression (control). Combinations were repeated every 14 days for up to eight cycles, followed by fluorouracil and leucovorin plus bevacizumab maintenance. The primary endpoint was progression-free survival 2, analysed by intention to treat. 679 patients were randomly assigned and received treatment (340 control, 339 experimental).
Primary endpoint
PFS2
Arms
  • mFOLFOX6 plus bevacizumab, then FOLFIRI plus bevacizumab (control, n = 340): First-line mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab after progression
  • FOLFOXIRI plus bevacizumab, then reintroduction (experimental, n = 339): First-line FOLFOXIRI plus bevacizumab followed by reintroduction of the same regimen after progression
People
Cremolini C
PFS2HR 0.74 (95% CI 0.63–0.88)Δ median PFS2+2.8 months
Show the numbers
Results reported for TRIBE2
EndpointAnalysisFOLFOXIRI plus bevacizumab, then reintroductionmFOLFOX6 plus bevacizumab, then FOLFIRI plus bevacizumabEffect
PFS2primarymedian follow-up 35.9 monthsCremolini 2020median 19.2 months (17.3–21.4)median 16.4 months (15.1–17.5)HR 0.74 (95% CI 0.63–0.88)P=0.0005Progression-free survival 2: time from randomisation to progression on any treatment given after first progression, or death.
Results reported for TRIBE2
EndpointAnalysisFOLFOXIRI plus bevacizumab, then reintroductionmFOLFOX6 plus bevacizumab, then FOLFIRI plus bevacizumabEffect
PFS2primarymedian follow-up 35.9 monthsCremolini 2020median 19.2 months (17.3–21.4)median 16.4 months (15.1–17.5)HR 0.74 (95% CI 0.63–0.88)P=0.0005Progression-free survival 2: time from randomisation to progression on any treatment given after first progression, or death.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS20.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS20.740.63–0.88
Illustrative — modelled from reported values, not trial data. PFS2, primary.
0%25%50%75%100%010203040Months (modelled)
  • FOLFOXIRI plus bevacizumab, then reintroduction (experimental)
  • mFOLFOX6 plus bevacizumab, then FOLFIRI plus bevacizumab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsFOLFOXIRI plus bevacizumab, then reintroductionmFOLFOX6 plus bevacizumab, then FOLFIRI plus bevacizumab
0100.0%100.0%
1264.8%60.2%
2442.0%36.3%
3627.3%21.8%
4817.7%13.2%
Primary publication: Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, et al. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020;21(4):497-507. PubMedDOI

Appears in

Sources

  1. Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, et al. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020;21(4):497-507.

    PubMedDOI