A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen (NCT00615056), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS).

2. Clinical Question

3. Trial Design

This was a randomized, phase 2, parallel-group study with no masking. The registry record lists enrollment of 171 participants and a completed status. It describes four treatment groups: axitinib plus FOLFIRI, bevacizumab plus FOLFIRI, axitinib plus FOLFOX, and bevacizumab plus FOLFOX. The comparisons pair treatments within the same chemotherapy backbone, allowing the axitinib and bevacizumab combinations to be considered separately for FOLFIRI and FOLFOX.

The primary outcome was progression-free survival, measured from the first dose of study medication to the first documentation of objective tumor progression or death from any cause. The registry description says tumor progression was determined from oncologic assessment data meeting the criteria for progressive disease, or from adverse-event data when the outcome was death. Assessments were described as occurring every 8 week up to 130 weeks. The analysis population included all randomized participants, assigned according to their initial randomization regardless of treatment received.

The record gives the four arm sizes as 49, 51, 36, and 35, respectively, for axitinib plus FOLFIRI, bevacizumab plus FOLFIRI, axitinib plus FOLFOX, and bevacizumab plus FOLFOX. Randomization and the parallel structure are reported, but the method used to generate or conceal the allocation sequence is not reported in the registry record. The registry record also does not report the planned allocation ratio, any stratification factors, or the trial’s original sample-size justification. It should not be assumed that the planning illustrations accompanying the posted results reproduce the study’s original design calculations.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival (PFS), measured over Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks.

Progression-free survival measures the time from the start of study medication until objective tumor progression is first documented or death from any cause occurs. It combines disease progression and death into a single time-to-event outcome. A participant’s event time is therefore determined by whichever of these events occurs first, according to the endpoint definition.

This type of endpoint is used to describe how long participants remain alive without documented progression during follow-up. It can incorporate information from different follow-up durations rather than reducing the outcome to whether progression occurred by one fixed date. The registry record specifies that progression was identified through oncologic assessment data meeting the criteria for progressive disease, or through adverse-event data recording death. It also gives the event-time calculation as the first event date minus the date of first dose of study medication plus 1, divided by 30.4, to express time in months.

The posted primary outcome reports medians with 95% confidence intervals for each treatment group. A median is the time by which half of the participants in the analyzed group have experienced the event, under the time-to-event analysis. It does not describe every participant’s course, and it does not alone quantify the relative comparison between treatment groups. The sponsor’s reported hazard ratios and their confidence intervals provide the comparative time-to-event summaries. The registry record does not report further details about censoring rules or how incomplete follow-up was handled, so those aspects cannot be assessed from the posted information.

7. Results Posted in the Registry

• Axitinib + FOLFIRI vs Bevacizumab + FOLFIRI: hazard ratio 1.27 (95% CI 0.77–2.11), reported p = 0.827 (as reported in the registry).
• Axitinib + FOLFOX vs Bevacizumab + FOLFOX: hazard ratio 1.04 (95% CI 0.55–1.04), reported p = 0.550 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Overall Survival (OS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Axitinib + FOLFIRI vs Bevacizumab + FOLFIRI: hazard ratio 1.35 (95% CI 0.82–2.24), reported p = 0.883 (as reported in the registry).
  • Axitinib + FOLFOX vs Bevacizumab + FOLFOX: hazard ratio 0.69 (95% CI 0.37–1.27), reported p = 0.116 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Axitinib + FOLFIRI vs Bevacizumab + FOLFIRI and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Axitinib + FOLFOX vs Bevacizumab + FOLFOX and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Objective Response (OR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Bevacizumab + FOLFIRI: 23.5% (12/51) versus 24.5% (12/49) on control; risk difference -1.0 percentage points (95% CI -17.7 to 15.8), risk ratio 0.96 (0.48–1.93); unadjusted two-proportion z-test p = 0.910.
  • Axitinib + FOLFOX: 19.4% (7/36) versus 24.5% (12/49) on control; risk difference -5.0 percentage points (95% CI -22.7 to 12.6), risk ratio 0.79 (0.35–1.82); unadjusted two-proportion z-test p = 0.581.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Bevacizumab + FOLFIRI and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Axitinib + FOLFOX and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results cover overall survival and objective response, while the listed secondary outcomes also include duration of response and changes in diarrhea symptom severity and symptom interference. The overall survival and objective-response results provide additional outcome-specific descriptions, but they do not replace the primary progression-free survival analysis. Overall survival concerns time until death, whereas response and response duration address tumor response in different ways. The diarrhea measures describe symptom scores rather than tumor progression or survival.

Across the available secondary comparisons, the estimates are accompanied by uncertainty, and the record does not establish a consistent, precise separation between axitinib and bevacizumab across the chemotherapy backbones. The pattern should be considered alongside the primary result, not as an independent confirmation of a treatment effect. Secondary endpoints can help describe the range of outcomes considered, but they may be less definitive when many outcomes or comparisons are assessed.

General statistical explanation: when several endpoints and group comparisons are examined, the chance of encountering a small p-value by chance can rise unless the analysis plan accounts for multiple testing. The registry record does not report a multiplicity adjustment or a prespecified testing hierarchy. Secondary p-values and estimates should therefore be interpreted cautiously and should not be treated as confirmatory evidence without knowing how the testing strategy was planned.

Although the record lists duration of response and the two diarrhea symptom measures among its secondary outcomes, their numerical results are not reported in the registry record. Their absence means the full secondary-outcome pattern cannot be evaluated from the posted results. The secondary findings that are reported offer context, but they do not resolve the uncertainty in the primary time-to-event comparisons.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Overall Survival (OS)
• Percentage of Participants With Objective Response (OR)
• Duration of Response (DR)
• Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal
• Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal

9. Statistical Interpretation

10. Statistical Methods Explained

Progression-free survival is a time-to-event outcome. Instead of comparing only the proportion of participants who experienced progression by a single selected time, a time-to-event analysis uses event timing and can account for participants whose full event time is not observed during follow-up. General statistical explanation: participants without a recorded event at the end of their observed follow-up are commonly treated as censored, but the registry record does not report the censoring rules used in this study. That omission limits a reader’s ability to reproduce or fully assess the analysis.

What does a median time-to-event value describe?

A median is a point on the estimated event-time distribution: half of the group is estimated to have experienced the event by that time. It is a summary of the group distribution, not a typical individual’s guaranteed experience or a comparison adjusted for other characteristics. The reported medians are accompanied by confidence intervals, which indicate uncertainty around the estimated median. The primary outcome’s stated time unit is months, and the record describes how event time was calculated from the first dose date and first event date.

What does a hazard ratio describe?

A hazard ratio compares the event rates over time between two groups under the time-to-event analysis. A value of 1 represents equal hazards in the comparison as represented by the model; values on either side represent different relative hazards. General statistical explanation: a hazard ratio is not a ratio of the two median survival times, and it does not directly state how many months an individual gains or loses. Its interpretation also depends on the statistical assumptions and analysis procedures used. The registry identifies the reported method as Log Rank and labels the comparison statistic as a hazard ratio, but further modeling details are not reported in the registry record.

The sponsor-reported primary comparisons are 1.273 for axitinib plus FOLFIRI versus bevacizumab plus FOLFIRI, and 1.041 for axitinib plus FOLFOX versus bevacizumab plus FOLFOX. Their respective reported 95% confidence intervals are 0.769 to 2.108 and 0.553 to 1.041. The associated p-values are 0.827 and 0.550. The estimates and intervals should be interpreted together: the point estimate alone gives no indication of how uncertain the comparison is, while the interval shows a broad range of effects compatible with the analysis.

How should the p-values be read?

A p-value summarizes how compatible the observed data are with a specified null model, given the statistical method and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure clinical importance. The reported values do not establish that the regimens are equivalent. Demonstrating equivalence or non-inferiority requires an appropriately specified design and margin; such information is not reported in the registry record. A failure to demonstrate a difference is not the same as evidence that two treatments have the same effect.

The record also reports objective response comparisons using Chi-squared analyses, as well as results for overall survival. Those outcomes are distinct from progression-free survival: overall survival concerns death, while objective response concerns the proportion meeting the response definition. Each endpoint has its own estimate and uncertainty. General statistical explanation: assessing several outcomes or comparisons can increase the chance of at least one apparently unusual result if no adjustment or prespecified hierarchy is used. The record does not report whether multiplicity was controlled, whether a hierarchy was planned, or whether any interim analyses were conducted. These procedures should not be inferred from the posted p-values.

The intent-to-treat population is defined as all randomized participants, with each analyzed according to initial assignment, regardless of whether study drug was received or a different drug was taken. This preserves the randomized assignment for the primary analysis as described in the record. It does not, by itself, explain how missing outcome data, treatment discontinuation, or protocol deviations were handled. Those details are not reported in the registry record. The study’s original statistical analysis plan and sample-size justification are also not reported, so the posted calculations cannot be taken as a substitute for them.

11. Confidence Intervals and Precision

The 95% confidence intervals show that the primary estimates are not precise enough to pin down a narrow range of comparative effects. In the FOLFIRI comparison, the median estimates are 5.72 months for axitinib plus FOLFIRI and 6.87 months for bevacizumab plus FOLFIRI, with intervals from 4.5 to 7.42 months and 4.96 to 9.13 months. The sponsor-reported hazard-ratio interval, 0.769 to 2.108, covers values on either side of 1. The result therefore leaves substantial uncertainty about the relative time-to-event effect.

In the FOLFOX comparison, the median estimates are 7.59 months and 6.44 months, with intervals from 5.62 to 11.07 months and 5.52 to 13.11 months. The reported hazard-ratio interval is 0.553 to 1.041. It includes 1 and is broad relative to the point estimate. Its upper limit matches the reported estimate of 1.041, a feature of the record that should be kept in mind when reading this comparison.

General statistical explanation: a confidence interval describes uncertainty under the statistical method; it is not a range that contains the true effect with a fixed probability after the data have been observed. Wider intervals indicate less precision, and overlapping intervals for separate group medians do not replace a direct comparison test. The sponsor-reported hazard ratios and p-values are the record’s direct comparative results. The available arm sizes are modest, and the intervals illustrate that point estimates should not be treated as exact or conclusive. The registry record does not report additional precision measures or detailed assumptions needed to evaluate the interval calculations independently.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations translate an observed effect into hypothetical sample-size requirements under stated assumptions; they do not describe the number of participants actually enrolled. For time-to-event outcomes, the figures are total events required across the two comparison groups, not participants per arm. For other outcomes, the figures are participants per arm. Thus the progression-free survival comparisons use total events, while an objective-response comparison uses participants per arm.

The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. The displayed scenarios for 100%, 75%, and 50% of the observed effect illustrate how planning changes when the target effect is smaller. Smaller effects require more information to detect under otherwise similar assumptions, so the corresponding planning requirements increase as the target effect is reduced.

For example, the FOLFIRI progression-free survival comparison lists 539 total events for 80% power and 722 total events for 90% power when planning for 100% of the observed effect. In the FOLFOX progression-free survival comparison, the corresponding figures are 19,446 and 26,032 total events. These are illustrations based on the posted observed effects, not the trial’s original enrollment target or design justification. The record does not report the original sample-size assumptions used to plan the study.

The 80% and 90% power columns describe the hypothetical chance of detecting the specified effect under the calculation’s assumptions if that effect were the true effect. The figures are planning illustrations, not observed power. They should not be interpreted as a retrospective measure of whether the trial succeeded or as proof that an effect exists.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.273, so ln(HR) = 0.2414.
2. d = 4 × (1.96 + 0.842)² / [ln(1.273)]² = 538.9, rounded up to 539 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.273                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(615056)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 539 (80% power), 722 (90% power)
 75% of observed effect: events = 958 (80% power), 1,283 (90% power)
 50% of observed effect: events = 2,156 (80% power), 2,886 (90% power)
Simulated power with 539 events: 0.792 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The primary time-to-event comparisons use the sponsor’s reported hazard ratios and Log Rank p-values. For axitinib plus FOLFIRI versus bevacizumab plus FOLFIRI, the reported hazard ratio is 1.273, its 95% confidence interval is 0.769 to 2.108, and the p-value is 0.827. For axitinib plus FOLFOX versus bevacizumab plus FOLFOX, the reported hazard ratio is 1.041, its 95% confidence interval is 0.553 to 1.041, and the p-value is 0.550. These are the registry’s comparative time-to-event analyses; no separate recalculated hazard ratio is used.

For objective response, the registry reports Chi-squared analyses. The comparison of axitinib plus FOLFIRI with bevacizumab plus FOLFIRI has a reported mean difference of 1, a 95% confidence interval from -15.8 to 17.7, and a p-value of 0.455. The corresponding FOLFOX comparison reports -0.6, with a 95% confidence interval from -19.1 to 18.0 and a p-value of 0.523. These are sponsor-reported analyses, not the same estimand or method as an unadjusted risk-difference recalculation.

The record does not flag a discrepancy between reported and recalculated results. Any simple unadjusted recalculation from posted summary statistics is distinct from the sponsor’s analysis and may use different methods or estimands. For the time-to-event outcomes, interpretation therefore rests on the sponsor-reported comparisons. The registry record does not provide the full analysis code or enough detail to reconstruct the sponsor’s analyses independently.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcomes and separate comparisons for the FOLFIRI and FOLFOX backbones. It does not report whether the primary comparisons were adjusted for multiplicity, whether the secondary outcomes followed a prespecified testing sequence, or whether any multiplicity procedure was used. Without that information, the reported p-values should be read as the results of the individual analyses rather than as evidence that a family-wise error rate was controlled. The record also does not report whether interim analyses were planned or conducted.

The primary analysis population is described as intent-to-treat and includes all randomized participants according to their initial assignment, regardless of whether they received study drug or received a different drug. This definition clarifies the treatment-assignment principle for the primary outcome. It does not provide the missing-data procedures, the censoring rules, or details about handling participants who discontinued treatment or had no evaluable outcome. These aspects are not reported in the registry record.

The original statistical analysis plan and the study’s sample-size justification are also not reported in the registry record. The planning illustrations based on observed effects do not establish what assumptions were used to design the trial. Details about allocation concealment, stratification, covariate adjustment, and prespecified subgroup analyses are likewise not reported in the registry record. They should not be inferred from the randomized, parallel-group design or from the analyses that are posted.

These omissions matter because analysis choices can influence interpretation, especially when there are multiple outcomes, incomplete follow-up, or different analysis populations. The reported results remain interpretable as registry-posted estimates, but a fuller assessment of bias control and analysis reproducibility would require the missing protocol and statistical-plan details.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (8.7%), diarrhoea (6.5%), disease progression (5.9%), abdominal pain (4.3%), nausea (4.3%).

The adverse-event results give counts of participants at risk and counts affected by serious adverse events or other adverse events for each treatment group. For axitinib plus FOLFIRI, 17 of 46 participants at risk were affected by a serious adverse event, and 45 of 46 were affected by another adverse event. For bevacizumab plus FOLFIRI, the corresponding counts were 9 of 51 and 51 of 51. For axitinib plus FOLFOX, they were 11 of 36 and 35 of 36; for bevacizumab plus FOLFOX, they were 5 of 35 and 33 of 35.

The record lists dehydration at 8.7%, diarrhoea at 6.5%, disease progression at 5.9%, and abdominal pain, nausea, and asthenia each at 4.3% among the top serious adverse-event terms. These term percentages should be read as registry-reported summaries; the record does not give enough information to determine whether terms overlap within participants. The death counts are not reported in the registry record.

These figures describe recorded adverse events in the listed groups. They do not by themselves establish that one regimen caused more harm than another: the groups differ in size, and the posted summaries do not give a comparative safety analysis or additional adjustment. The safety information should be interpreted as descriptive rather than as a complete assessment of comparative safety.

17. What the Result Does, and Does Not, Mean

The posted primary results describe progression-free survival in four treatment groups and provide two comparisons within chemotherapy backbones. They show median estimates and sponsor-reported hazard ratios with confidence intervals and p-values. The intervals are broad, and the comparative estimates do not establish a clear separation between axitinib and bevacizumab for either the FOLFIRI or FOLFOX combination. This is a statement about the uncertainty in the posted analyses, not proof that the regimens have identical effects.

The results also do not establish equivalence or non-inferiority. Those conclusions require a design and analysis that specify an appropriate margin and testing approach. Such details are not reported in the registry record. Nor do the results establish that the findings apply to patients outside the registered population or to treatment settings not described in the record.

The medians are group-level summaries, not predictions for an individual participant. A hazard ratio summarizes relative event rates over time under the analysis; it does not state a guaranteed change in months for an individual. The secondary results add information about other outcomes, but the available registry record does not report numerical findings for every listed secondary endpoint, and it does not describe a multiplicity strategy.

Finally, the planning illustrations are hypothetical calculations based on observed effects and stated assumptions. They are not the original design justification and do not measure the trial’s observed power. The registry record does not report several details needed for a full independent appraisal, including missing-data procedures and the statistical analysis plan. The most defensible reading is therefore limited to the estimates and uncertainty reported for this randomized phase 2 study.

18. Why This Trial Matters Statistically

This study illustrates why trial comparisons should be interpreted within the treatment structure that was randomized. Axitinib was paired with two different chemotherapy backbones, and each pairing was compared with the corresponding bevacizumab combination. The two comparisons have separate estimates and uncertainty; collapsing them into a single statement would obscure that structure.

It also demonstrates the distinction between descriptive arm summaries and direct comparative analyses. Median progression-free survival gives a useful summary for each group, while the hazard ratio and Log Rank test provide the registry’s comparative time-to-event results. Confidence intervals are essential to judging how much uncertainty surrounds both kinds of estimates. Point estimates alone can appear more decisive than the data support.

The record further shows why planning illustrations need careful interpretation. Calculations based on an observed effect can produce very different sample-size requirements depending on the target effect and outcome type. They are not evidence that the original trial was designed around those numbers, and they are not a retrospective measure of power. The original planning assumptions are not reported.

Finally, the trial highlights the importance of transparent reporting beyond headline results. The intent-to-treat population is defined, but key details about missing data, multiplicity, and the analysis plan are absent from the registry record. These gaps do not erase the posted findings; they define the limits of what can be concluded from them.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary comparison results are imprecise, with broad confidence intervals for the reported hazard ratios and median progression-free survival estimates. The FOLFOX hazard-ratio interval is reported as 0.553 to 1.041 around an estimate of 1.041; the record does not explain this feature. The arm sizes are also uneven across the four groups, and the registry does not describe the allocation ratio or explain the group-size pattern.

The registry record does not report the original sample-size justification, statistical analysis plan, censoring rules, or procedures for handling missing data and treatment discontinuation. It also does not report multiplicity control or whether interim analyses were performed. Those omissions restrict assessment of how the analyses were planned and how robust the findings are to analytic choices.

Some listed secondary outcomes do not have numerical results reported in the registry record, including duration of response and the diarrhea symptom severity and interference measures. The safety summaries are descriptive; deaths are not reported in the registry record, and no comparative safety analysis is described in the posted information. The record also does not provide enough detail to reconstruct the sponsor’s analyses independently.

These limitations call for cautious interpretation of the reported estimates. They do not imply that the results are invalid, but they prevent a complete evaluation of precision, analysis choices, and the broader outcome pattern from the registry record alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen — NCT00615056.
• Registry record last updated 2013-04-19; status last verified 2013-04.
• Results first posted 2012-04-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry record describes a completed randomized phase 2 study with 171 participants and no masking. It compared axitinib, also identified as AG-013736, plus FOLFIRI or FOLFOX with bevacizumab plus the corresponding chemotherapy. The primary outcome was progression-free survival in the intent-to-treat population.

The posted median progression-free survival estimates differed across groups, while the sponsor-reported hazard-ratio comparisons were imprecise and did not establish a clear separation for either chemotherapy backbone. Overall survival and objective response are among the secondary outcomes with posted results; several other listed secondary outcomes do not have numerical results reported in the registry record.

Interpretation is limited by broad uncertainty and by unreported details about the original design assumptions, missing-data handling, multiplicity, and analysis plan. The sample-size illustrations are planning calculations based on observed effects, not the trial’s original design justification or observed power.