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Bending the Curve Trial by Trial
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TRIBE

A PHASE III RANDOMIZED TRIAL OF FOLFOXIRI + BEVACIZUMAB VERSUS FOLFIRI + BEVACIZUMAB AS FIRST- LINE TREATMENT FOR METASTATIC COLORECTAL CANCER

Phase 3N = 508NCT00719797

Population
Previously untreated unresectable metastatic colorectal cancer
Design
Open-label, multicentre phase 3 trial in Italy (34 oncology units per the 2015 report) in patients with unresectable, untreated metastatic colorectal cancer (aged 18 to 70 years with ECOG performance status 2 or less, or aged 71 to 75 years with performance status 0, per the 2015 report). Patients were randomly assigned (1:1) to FOLFIRI plus bevacizumab (control) or FOLFOXIRI plus bevacizumab (experimental) for up to 12 cycles, followed by fluorouracil plus bevacizumab until progression. The primary endpoint was progression-free survival. 508 patients were randomly assigned (July 2008 to May 2011).
Primary endpoint
PFS
Arms
  • FOLFIRI plus bevacizumab (control): FOLFIRI plus bevacizumab 5 mg per kilogram, up to 12 cycles then fluorouracil plus bevacizumab
  • FOLFOXIRI plus bevacizumab (experimental): FOLFOXIRI plus bevacizumab 5 mg per kilogram, up to 12 cycles then fluorouracil plus bevacizumab
People
Loupakis F
PFSHR 0.75 (95% CI 0.62–0.90)Δ median PFS+2.4 monthsΔ ORR+12 pointsOSHR 0.79 (95% CI 0.63–1.00)Δ median OS+5.2 monthsOSHR 0.80 (95% CI 0.65–0.98)
Show the numbers
Results reported for TRIBE
EndpointAnalysisFOLFOXIRI plus bevacizumabFOLFIRI plus bevacizumabEffect
PFSAll randomised patients (analysis population not stated in the abstract)primaryLoupakis 2014median 12.1 monthsmedian 9.7 monthsHR 0.75 (95% CI 0.62–0.90)P=0.003Primary endpoint.
ORRAll randomised patients (analysis population not stated in the abstract)primaryLoupakis 201465%53%P=0.006
OSAll randomised patients (analysis population not stated in the abstract)primaryLoupakis 2014median 31 monthsmedian 25.8 monthsHR 0.79 (95% CI 0.63–1.00)P=0.054The abstract states that overall survival was longer, but not significantly so, in the experimental group.
OSlong term-updatemedian follow-up 48.1 monthsCremolini 2015median 29.8 months (26.0–34.3)median 25.8 months (22.5–29.1)HR 0.80 (95% CI 0.65–0.98)P=0.03Updated overall survival (secondary endpoint) from the same trial after longer follow-up; all analyses by intention to treat per the abstract.
Results reported for TRIBE
EndpointAnalysisFOLFOXIRI plus bevacizumabFOLFIRI plus bevacizumabEffect
PFSAll randomised patients (analysis population not stated in the abstract)primaryLoupakis 2014median 12.1 monthsmedian 9.7 monthsHR 0.75 (95% CI 0.62–0.90)P=0.003Primary endpoint.
ORRAll randomised patients (analysis population not stated in the abstract)primaryLoupakis 201465%53%P=0.006
OSAll randomised patients (analysis population not stated in the abstract)primaryLoupakis 2014median 31 monthsmedian 25.8 monthsHR 0.79 (95% CI 0.63–1.00)P=0.054The abstract states that overall survival was longer, but not significantly so, in the experimental group.
OSlong term-updatemedian follow-up 48.1 monthsCremolini 2015median 29.8 months (26.0–34.3)median 25.8 months (22.5–29.1)HR 0.80 (95% CI 0.65–0.98)P=0.03Updated overall survival (secondary endpoint) from the same trial after longer follow-up; all analyses by intention to treat per the abstract.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.750.62–0.9
OS0.790.63–1
OS0.80.65–0.98
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • FOLFOXIRI plus bevacizumab (experimental)
  • 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 bevacizumabFOLFIRI plus bevacizumab
0100.0%100.0%
863.2%56.5%
1542.3%34.2%
2326.8%19.3%
3017.9%11.7%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0204060Months (modelled)
  • FOLFOXIRI plus bevacizumab (experimental)
  • 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 bevacizumabFOLFIRI plus bevacizumab
0100.0%100.0%
1965.4%60.0%
3941.8%35.1%
5827.3%21.1%
7817.5%12.3%
Primary publication: Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609-18. PubMedDOI

Appears in

Sources

  1. Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609-18.

    PubMedDOI

  2. Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306-15.

    PubMedDOI