PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (NCT00364013), a randomized phase 3 study. The primary outcome is Progression-free Survival.

2. Clinical Question

3. Trial Design

PRIME was a randomized, parallel-group, unmasked phase 3 study. Its official title describes a multicenter comparison in previously untreated metastatic colorectal cancer. The registry record lists an enrollment of 1183 and a completed status. The recorded study start was 2006-08-01, and the primary completion date was 2009-08-01.

Participants were assigned to FOLFOX plus panitumumab or FOLFOX alone. The combination regimen used panitumumab at 6 mg/kg on Day 1 and FOLFOX on Days 1 and 2 of each 14-day cycle. FOLFOX alone was also administered on Days 1 and 2 of each 14-day cycle. Both regimens continued until disease progression or unacceptable toxicity.

The primary endpoint was progression-free survival, analyzed in the KRAS Efficacy Analysis Set, defined in the record as participants for whom KRAS status was assessed. The endpoint results were divided into wild-type KRAS and mutant KRAS groups. The record reports medians and 95% confidence intervals for each treatment group, plus a stratified log-rank test within each KRAS category. It does not report the details of the stratification factors.

The primary endpoint timeframe ran from randomization to the data cutoff date of 30 September 2008; maximum follow-up time was 109 weeks. The registry lists overall survival, objective response, time to progression, duration of response, and adverse events among the secondary outcomes. Results are available for objective response and adverse-event counts in the posted information; numerical results for the other listed secondary outcomes are not reported in the registry record.

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: KRAS Efficacy Analysis Set (participants for whom KRAS status was assessed)

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, measured over From randomization until the data cutoff date of 30 September 2008. Maximum follow-up time was 109 weeks..

Progression-free survival measures the time from randomization until disease progression or death. In this study, progression was assessed by central radiological review using modified RECIST criteria. The registry description defines progressive disease as a ≥ 20% increase in target-lesion size, unequivocal progression of existing non-target lesions, or any new lesions.

This time-to-event endpoint incorporates both how long participants remain alive without documented progression and the timing of events. The median is the point at which the estimated progression-free survival distribution reaches its midpoint. It is not the average duration for all participants, and it does not describe the outcome of every individual. The reported confidence interval conveys uncertainty around the estimated median.

Some participants were alive without progression at the data cutoff. Under the stated endpoint definition, they were censored at their last evaluable disease assessment date. Censoring means that their observed follow-up contributes information up to that date, but the exact later time to progression or death is not known in the analysis.

Progression-free survival is useful for comparing the timing of disease progression or death within the observed follow-up period. It does not, on its own, establish an effect on overall survival, quality of life, or any other outcome. Overall survival is listed as a secondary outcome, but numerical overall-survival results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median time-to-event result mean?

Progression-free survival is a time-to-event outcome because the analysis concerns the time until progression or death. A median summarizes the estimated distribution: it marks the time by which half of the analyzed population is estimated to have experienced the event. It does not mean that every participant experienced progression or death at that time, and it is not an arithmetic average.

Time-to-event methods can include participants whose event has not yet been observed by the analysis cutoff. In this trial, participants who were alive and did not meet the progression criteria by the cutoff were censored at their last evaluable disease assessment. Such participants contribute information through their observed follow-up, while their later event time remains unknown. The interpretation relies on the analysis appropriately accounting for this incomplete follow-up.

How should the confidence intervals be read?

The registry reports a 95% confidence interval for each median. A confidence interval expresses uncertainty in an estimate under the statistical method used: it gives a range of values compatible with the data and method, rather than a guarantee that the true value lies in that particular interval. The intervals attached to each arm’s median are not intervals for a treatment contrast. Comparing their endpoints informally is not a substitute for a direct treatment-effect estimate with its own uncertainty interval.

The registry record does not report confidence intervals for a primary hazard ratio or other direct measure of the contrast between arms. The reported log-rank tests provide a test statistic and p-value for each within-KRAS comparison, but they do not supply a direct estimate of the size of the treatment contrast.

What does the stratified log-rank test assess?

A log-rank test compares the event-time experience of groups over follow-up, taking account of the timing of events and censored observations. A stratified version performs the comparison while allowing for specified strata. The registry identifies the method as a stratified log-rank test, but the stratification variables are not reported in the registry record. The reported normal score is the test statistic; it is not a difference in median survival time or a hazard ratio.

A p-value evaluates how compatible the observed test result is with a null hypothesis under the test’s assumptions. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of an effect. The sponsor’s reported p-values relate to the stratified tests; they should be understood in the context of the endpoint definition, analysis population, and any multiplicity considerations, which are not fully described in the registry record.

Why separate the KRAS categories?

The posted primary summaries divide participants into wild-type and mutant KRAS groups. Reporting each category separately makes the observed patterns visible, but the existence of separate results does not prove that treatment effects differ between the categories. A formal interaction analysis would address whether the contrast varies by KRAS status. Such a result is not reported in the registry record.

Subgroup results can also be less precise than an overall analysis because they concern subsets of the study population. The reported group sizes and confidence intervals help show the amount of information available for each estimate, but they do not resolve every issue of subgroup interpretation. The record does not report whether subgroup analyses were prespecified or how the analyses were prioritized.

How do the objective-response recalculations differ?

For objective response, the posted summary includes recalculated, unadjusted comparisons based on the displayed response proportions. These are descriptive re-calculations from summary statistics, not the sponsor’s stratified exact tests. An unadjusted calculation does not account for stratification or other possible design features. It should therefore be kept distinct from the sponsor’s own analysis.

The planning illustrations associated with the recalculated binary comparisons use a two-sided significance level of 0.05, equal allocation, and a normal approximation. They illustrate participants per arm for 80% or 90% power when the effect to detect is a stated fraction of the observed effect. They are not observed power, do not establish what the original trial was designed to detect, and are not the trial’s own sample-size justification. The registry record does not report that justification.

What are the limits of the posted methods?

The registry gives a primary endpoint definition, an analysis population, group summaries, and the sponsor’s test results. It does not report a full statistical analysis plan, the stratification variables, a hazard-ratio estimate, or a formal KRAS interaction result. It also does not report whether interim analyses were conducted or how missing data beyond the stated censoring rule were handled. These omissions limit how fully an external reader can reconstruct the analysis and assess its prespecification.

10. Analyses Reported by the Sponsor

For progression-free survival, the sponsor reports stratified log-rank tests separately for the wild-type and mutant KRAS groups. The reported normal scores are -2.27 and 2.28, respectively; the corresponding reported p-values are 0.023 and 0.023. These tests assess time-to-event distributions and are not direct estimates of a difference between medians. The registry does not report a hazard ratio or confidence interval for these primary comparisons.

The objective-response analyses reported by the sponsor use a stratified exact test and report odds ratios with 95% confidence intervals. The simple recalculations are unadjusted comparisons derived from posted summary proportions. Because the methods and adjustment differ, their estimates and p-values need not match the sponsor’s results. They answer related but not identical statistical questions.

The discrepancy flag is false, so the record does not identify a discrepancy between the posted sponsor analysis and the recalculation. The sponsor’s analyses remain the trial’s reported analyses; the recalculations are supplementary descriptions rather than replacements. Neither type of analysis should be read without considering the outcome definition, analysis population, uncertainty, and the absence of reported details about multiplicity and the full analysis plan.

11. Multiplicity, Missing Data and Analysis Populations

The primary progression-free survival results are reported separately for wild-type and mutant KRAS. Objective response is also reported in both KRAS categories, and the registry lists several additional secondary outcomes. Considering multiple outcomes and subgroup comparisons raises a multiplicity issue: without an adjustment or a prespecified testing hierarchy, isolated p-values can be less conclusive than a single primary test considered on its own. A multiplicity adjustment or hierarchy is not reported in the registry record.

The registry record does not report whether interim analyses were conducted, whether subgroup analyses were prespecified, or what sample-size justification was used. It also does not provide a complete statistical analysis plan. Those details would help readers understand which comparisons were confirmatory, how analyses were ordered, and whether any adjustments were planned. Their absence from the record does not establish that no such plans existed; it means they are not reported in the registry record.

The stated primary analysis population was the KRAS Efficacy Analysis Set, defined as participants for whom KRAS status was assessed. The record does not describe the disposition of participants without assessed KRAS status or provide a comparison with an all-randomized analysis. The group sizes for the primary endpoint are reported within each KRAS and treatment category.

For progression-free survival, the record states that participants alive without progression at the cutoff were censored at their last evaluable disease assessment. It does not report further sensitivity analyses for censoring or other missing-data procedures. The objective-response results include analysis denominators, but broader details about missing response assessments are not reported. These limits matter because the handling of unavailable outcome information can affect the interpretation of estimates and tests.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea (9.9%), dehydration (3.4%), intestinal obstruction (3.1%), vomiting (3.1%), pyrexia (2.7%).

The registry reports serious adverse events in groups labeled Panitumumab Plus FOLFOX and FOLFOX Alone. The serious-event group counts are 262 affected among 585 at risk in the combination group, and 198 affected among 584 at risk in the FOLFOX-alone group. The posted counts for participants affected by any adverse event are 577 among 585 at risk and 571 among 584 at risk, respectively. These are counts, not adjusted comparisons; the registry record does not provide a statistical test or confidence interval for these group differences.

The most frequently listed serious adverse-event terms include diarrhoea (9.9%), dehydration (3.4%), intestinal obstruction (3.1%), vomiting (3.1%), pyrexia (2.7%), and febrile neutropenia (2.6%). The registry does not explain in this summary whether participants could contribute to more than one term, so these percentages should not be added or treated as mutually exclusive categories. Death counts are not reported in the registry record.

Adverse-event counts describe events recorded during the trial; they do not by themselves establish that a particular event was caused by treatment. Differences in follow-up, event definitions, and reporting also affect interpretation. The registry record’s safety information should be read as descriptive rather than as a complete comparative safety analysis.

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

The posted primary results show different observed progression-free survival patterns across the two KRAS categories. In the wild-type group, the combination arm had a higher reported median than the FOLFOX-alone arm; in the mutant group, the combination arm had a lower reported median. The sponsor’s stratified log-rank tests also differ in direction across the subgroups. These are descriptions of the reported analyses, not a formal test that KRAS status modifies the treatment effect.

The results do not, by themselves, quantify how treatment changes the chance of progression or death at a particular time. The registry does not report primary hazard ratios or confidence intervals for the between-arm contrasts. Nor do the subgroup medians establish the magnitude of a treatment effect for an individual participant. The confidence intervals concern the arm-specific medians, not a direct difference between arms.

Progression-free survival is not interchangeable with overall survival. Although overall survival is listed among secondary outcomes, numerical overall-survival results are not reported in the registry record. The primary findings therefore do not establish an effect on length of life, quality of life, or any other outcome that is not reported.

The results apply to the stated analysis population and follow-up: participants with assessed KRAS status, with progression-free survival followed from randomization through the cutoff date of 30 September 2008 and maximum follow-up time of 109 weeks. Censoring and the available registry detail place limits on how much can be inferred. These findings should be understood as trial statistics, not as individualized guidance or a recommendation about treatment.

14. Why This Trial Matters Statistically

This trial illustrates why subgroup results and overall treatment summaries need careful separation. The primary endpoint is reported independently in wild-type and mutant KRAS groups, and the observed median patterns go in different directions. That makes it especially important not to infer that the subgroup effects differ merely because the within-subgroup results are not alike. A formal interaction analysis would be needed to directly test variation by KRAS status, and such a result is not reported in the registry record.

It also demonstrates the distinction between a time-to-event test and a comparison of medians. The sponsor used stratified log-rank tests, which evaluate event-time distributions while accounting for censoring and specified strata. The reported medians are accessible summaries, but they do not capture the full time-to-event comparison. A direct effect estimate and uncertainty interval would provide additional information, yet these are not reported for the primary comparisons.

The record further shows why endpoint populations, data cutoffs, and analysis plans matter. The primary summaries are based on the KRAS Efficacy Analysis Set, and the follow-up was limited by the stated cutoff. Some details that could strengthen interpretation—such as the stratification factors, multiplicity approach, and a formal interaction test—are not reported. Statistical conclusions depend not only on values, but also on what was measured, in whom, and under which analysis.

Finally, the trial’s objective-response recalculations illustrate the difference between a simple unadjusted analysis and a sponsor-reported stratified method. Treating those calculations as equivalent would blur distinct assumptions and questions. This is a useful reminder that numerical summaries need to be read together with their methods and limitations.

15. 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 registry record gives arm-specific medians and confidence intervals for progression-free survival, but it does not report a hazard ratio or confidence interval for either primary treatment comparison. The sponsor’s log-rank results test event-time distributions but do not supply a direct estimate of the size of the contrast. This limits assessment of the magnitude and precision of the between-arm effect.

Results are separated by KRAS status, but a formal interaction test is not reported. Without that analysis, the observed differences between subgroup patterns cannot establish that treatment effects truly vary by KRAS category. The record also does not report whether these subgroup analyses were prespecified.

The primary analysis population is defined as participants for whom KRAS status was assessed. The record does not explain the treatment of participants whose KRAS status was unavailable or show how this analysis population relates to all randomized participants. For progression-free survival, the stated censoring rule is available, but additional sensitivity analyses and broader missing-data procedures are not reported.

The registry lists several secondary outcomes, but numerical results for overall survival, time to progression, and duration of response are not reported in the registry record. Nor is a multiplicity adjustment or testing hierarchy reported. The full statistical analysis plan, stratification factors, interim-analysis details, and sample-size justification are also not reported in the registry record.

Finally, the follow-up description is tied to the data cutoff date of 30 September 2008, with maximum follow-up time of 109 weeks. The posted results therefore reflect that analysis window rather than later follow-up. These reporting limits do not invalidate the reported analyses, but they constrain independent evaluation and the scope of conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy — NCT00364013.
• Registry record last updated 2022-11-07; status last verified 2022-11.
• Results first posted 2014-03-28.
• 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.

19. Record Summary

PRIME was a randomized, unmasked, parallel-group phase 3 study in previously untreated metastatic colorectal cancer. It compared panitumumab plus FOLFOX with FOLFOX alone. The primary outcome was centrally assessed progression-free survival in participants with assessed KRAS status, reported separately for wild-type and mutant KRAS.

The wild-type group had a higher reported median progression-free survival in the combination arm, while the mutant group had a lower reported median in that arm. Sponsor-reported stratified log-rank tests were reported for both comparisons. The registry also contains objective-response analyses and adverse-event counts, but does not provide numerical results for several listed secondary outcomes.

Interpretation is limited by the absence of primary hazard-ratio estimates, a formal KRAS interaction result, and reported details on multiplicity, interim analyses, and the full statistical plan. The posted statistics describe the defined outcomes, populations, and follow-up; they do not establish effects on outcomes for which results are not reported.