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Metastatic Colorectal Cancer
Phase 3
NCT00719797

TRIBE: Complete Statistical Analysis of FOLFOXIRI Plus Bevacizumab in Metastatic Colorectal Cancer

An independent statistical analysis of the randomized phase 3 TRIBE trial evaluating bevacizumab with oxaliplatin, irinotecan, and infusional 5FU/LV (GONO FOLFOXIRI regimen) compared with bevacizumab with irinotecan and infusional 5FU/LV (FOLFIRI regimen) as first-line therapy in metastatic colorectal cancer.

Scope of this record

This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.

1. Trial at a Glance

TRIBE was a phase 3 randomized parallel-group treatment trial sponsored by Gruppo Oncologico del Nord-Ovest evaluating combination chemotherapy strategies with bevacizumab in patients with colorectal cancer.

509
Enrollment
2
Arms
Phase 3
Trial Phase
54 months
Primary endpoint timeframe
FeatureTRIBE
ConditionColorectal Cancer
AllocationRandomized
Design modelParallel
MaskingNone
Primary purposeTreatment
Start date2008-07
Primary completion date2011-05

2. Clinical Question

Population

Patients with colorectal cancer enrolled in a first-line metastatic colorectal cancer treatment study.

Intervention

Bevacizumab combined with oxaliplatin, irinotecan, and infusional 5FU/LV (GONO FOLFOXIRI regimen).

Comparator

Bevacizumab combined with irinotecan and infusional 5FU/LV (FOLFIRI regimen).

Primary question

Does the FOLFOXIRI-based bevacizumab regimen improve progression-free survival compared with the FOLFIRI-based bevacizumab regimen?

3. Trial Design

Randomization

Patients were allocated randomly.

Structure

Parallel-group phase 3 treatment comparison.

ArmRegimen
ExperimentalBevacizumab + oxaliplatin + irinotecan + infusional 5FU/LV (GONO FOLFOXIRI).
ComparatorBevacizumab + irinotecan + infusional 5FU/LV (FOLFIRI).

4. Primary Endpoint

EndpointDefinitionTime frame
Progression free survivalCompare progression free survival between bevacizumab with GONO FOLFOXIRI and bevacizumab with FOLFIRI.Up to 54 months

5. Statistical Methodology

The primary endpoint is progression-free survival, a time-to-event outcome. These endpoints are typically analyzed by methods that account for incomplete follow-up, because some participants may not have experienced progression or death at the time of analysis.

Time-to-event framework

Progression-free survival analysis generally estimates the distribution of time until progression or death while accounting for censored observations.

A randomized comparison of progression-free survival commonly uses Kaplan-Meier estimation to describe event-free probability over time and Cox proportional-hazards models to estimate relative treatment effects. The ClinicalTrials.gov record does not report the formal statistical analyses or results for this endpoint.

6. Planned Analysis

The registry identifies progression-free survival as the primary endpoint and describes the comparison between the two bevacizumab-containing chemotherapy strategies. No formal statistical analyses were posted to ClinicalTrials.gov.

For a progression-free survival endpoint, a typical analysis would compare time to progression or death between randomized groups using survival analysis methods. The interpretation would focus on the estimated difference between treatment strategies, uncertainty around that estimate, and assumptions underlying the survival model.

7. Statistical Methods Explained

Why is progression-free survival analyzed as a time-to-event endpoint?

Patients experience progression or death at different times. A time-to-event framework incorporates both event times and patients whose outcomes are not yet observed at analysis.

What does censoring mean in progression-free survival?

Censoring means that follow-up information ends before the event occurs. Proper statistical methods use available follow-up without assuming that censored patients experienced an event at the last observation time.

Why is randomization important?

Randomization helps create comparable treatment groups at baseline, reducing bias when comparing outcomes between treatment strategies.

Why is a hazard ratio often used for survival endpoints?

A hazard ratio summarizes the relative event rate between groups over the analyzed follow-up period. It does not directly represent the probability that an individual patient will experience an event.

Why are confidence intervals important?

Confidence intervals describe uncertainty around an estimated treatment effect and help distinguish precise estimates from those with substantial uncertainty.

8. Limitations

9. Why This Trial Matters Statistically

ConceptHow it appears in TRIBE
RandomizationRandomized phase 3 parallel-group comparison.
Time-to-event analysisPrimary endpoint was progression-free survival.
Comparative effectivenessTwo bevacizumab-containing chemotherapy strategies were compared.
Clinical trial designTreatment allocation and endpoint definitions were prespecified in the registry.

10. Sources