Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer (A ComboMATCH Treatment Trial): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer (A ComboMATCH Treatment Trial) (NCT05554354), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS) (Cohort I).

2. Clinical Question

3. Trial Design

This was a phase II, randomized, parallel-group trial sponsored by the National Cancer Institute. The registry reports no masking. Its stated purpose was to compare usual treatment with fulvestrant alone against the addition of binimetinib in patients with hormone receptor-positive metastatic breast cancer with an NF1 genetic change. The primary comparison was defined for Cohort I, with progression-free survival as the primary endpoint.

The Cohort I descriptions identify an arm receiving fulvestrant and binimetinib and an arm receiving fulvestrant alone. The record also describes Cohort II with fulvestrant and binimetinib, and says that participants progressing on fulvestrant alone might migrate to that cohort if they met eligibility criteria. The relationship between these cohorts and the full allocation process is not completely described in the available record. The eligibility criteria for migration are not reported in the registry record.

The registry lists a start date of 2024-09-13 and a primary completion date of 2025-04-04. Its status is terminated, and it reports enrollment of 1 participant. No reason for termination is reported in the registry record. The record also does not report whether treatment was initiated, the assigned arm, treatment duration, or follow-up for the enrolled participant.

The planned endpoint assessment used the time from randomization to progression or death from any cause, whichever came first, assessed up to 5 years. The registry describes a one-sided log-rank test with alpha=0.1, a Kaplan-Meier plot, and estimation of a hazard ratio with a 95% confidence interval using a Cox proportional model with treatment as a covariate. These are descriptions of intended analysis methods, not completed analyses. No analysis results are reported, and the record does not describe changes to the design after enrollment.

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.

Before assignment: The study was terminated. Only 1 participant was enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The study was terminated. Only 1 participant was enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

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.

Population: The study was terminated. Only 1 participant was enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival (PFS) (Cohort I), measured over The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years.

Progression-free survival (PFS) is the primary endpoint for Cohort I. The registry defines it as the duration between randomization and progression or death from any cause, whichever happens first, with assessment planned up to 5 years. This endpoint combines disease progression and death into a time-to-event measure. A participant’s time contributes until the first qualifying event or, if no event is observed during follow-up, until the last available assessment under the analysis rules. The precise censoring rules are not reported in the registry record.

In general, PFS is used in clinical trials to describe how long participants remain alive without documented progression. Comparing time-to-event distributions can use information about both when events occur and how long participants are followed. This is different from comparing only the number of participants with an event at a single assessment time. The endpoint is relevant to the trial’s stated question because the registry describes an aim of comparing the time tumors remain stable between the treatment strategies.

The registry planned a log-rank comparison and a Cox-model hazard ratio, with a Kaplan-Meier plot. Those methods can describe differences in event timing, but they require observed outcome and follow-up data to produce an interpretable estimate. No PFS observations or effect estimates are reported. The stated follow-up horizon is part of the endpoint definition; it does not establish that participants were followed for that duration.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry outlines methods for a time-to-event comparison but does not report completed analyses. The methods can be understood as a plan for analyzing PFS if suitable follow-up and event data are available. They should not be confused with results. No test statistic, estimate, confidence interval, or plot values are reported for the trial.

What does the log-rank test compare?

In general, a log-rank test compares the observed timing of events between groups over follow-up. For this trial, the event was defined as progression or death from any cause, whichever happened first. The test uses event timing and the numbers still at risk at relevant points in follow-up, rather than reducing the comparison to a single endpoint count. It is commonly used for comparing time-to-event outcomes when the groups’ event experience is evaluated across the follow-up period.

The registry specifies a one-sided test with alpha=0.1. A significance level is a threshold chosen in advance for judging a test result under its statistical assumptions. A one-sided test addresses a prespecified direction of difference; the registry does not state the direction in the method description. Without a test result and a clearly reported direction, the chosen threshold cannot support a conclusion. The record does not report whether the planned test was carried out.

What would a Kaplan-Meier estimate show?

In general, the Kaplan-Meier method estimates the probability of remaining event-free over time while accounting for participants whose event status is not observed through the full follow-up period. Such participants may be censored at the last time their status is known, depending on the analysis rules. A Kaplan-Meier curve can display the estimated event-free experience over time and show when events and censoring occur. The registry says a plot would be provided, but no PFS plot or curve estimates are reported. The specific censoring rules and assessment schedule are not reported in the registry record.

How is a hazard ratio used?

In general, a hazard ratio compares the event rates between groups over follow-up, conditional on remaining event-free up to each time. A Cox proportional hazards model can estimate this ratio while accounting for event times and censoring. The registry describes treatment as the model covariate and calls for a corresponding 95% confidence interval. A confidence interval communicates uncertainty around an estimate: a narrower interval indicates greater precision, while a wider interval indicates less precision, under the model and sampling assumptions. No hazard ratio or confidence interval is reported, so neither the size nor the precision of a treatment contrast can be assessed.

The Cox model is based on assumptions, including proportional hazards: broadly, that the relative event rate between groups is reasonably stable over time. The record does not report any assessment of that assumption, any alternative model, or any adjustment for other covariates. With no posted outcome data, it is not possible to assess whether the model would have been suitable for the observed data.

Why does follow-up and censoring matter?

Time-to-event analyses depend on knowing when participants enter observation, when events occur, and when follow-up ends without a recorded event. Censoring allows participants with incomplete follow-up to contribute information up to the point when their event status is last known. In general, valid interpretation depends on appropriate censoring rules and on assumptions about the relation between censoring and the event process. The registry defines the PFS event and states an assessment horizon, but does not report the detailed censoring approach, actual follow-up, or event dates.

The record’s enrollment of 1 participant and its privacy-based non-reporting mean there is no usable basis for applying or checking these methods. The analysis description communicates what was planned; it does not establish that estimates were calculated or that a treatment effect was observed. The registry reports 0 analyses, and no completed statistical analysis is available to interpret.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes beyond the primary PFS endpoint in Cohort I. These include objective response rate for each Cohort I arm, objective response rate in Cohort II, clinical benefit rate, PFS in Cohort II, overall survival, and adverse-event incidence. Considering multiple endpoints or comparisons can increase the chance of at least one apparently notable finding when many tests are performed. In general, multiplicity can be addressed through prespecified testing hierarchies or statistical adjustment, but the record does not report such a strategy.

The primary endpoint description specifies a one-sided log-rank test with alpha=0.1. It does not describe how that test relates to tests of secondary outcomes, nor whether any adjustment or gatekeeping plan was intended. A multiplicity strategy is therefore not reported in the registry record. The record lists 0 analyses, and no endpoint-level analysis results are available.

Handling of missing outcome data is also not reported in the registry record. For PFS, the registry defines the event and assessment horizon but does not specify censoring rules, how incomplete assessments would be handled, or whether any sensitivity analyses were planned. The analysis populations are not reported: the record does not describe an intention-to-treat, per-protocol, or safety population for completed analyses. With only 1 participant enrolled and no outcome data reported for privacy, those omissions cannot be resolved from the posted results.

The record’s non-reporting of results should not be treated as a particular missing-data method. There are no reported endpoint estimates to which a missingness adjustment can be applied. Likewise, the absence of a reported multiplicity procedure does not establish that none was considered; it means the procedure is not reported in the registry record.

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

The registry record documents a phase II randomized trial intended to compare fulvestrant plus binimetinib with fulvestrant alone for patients with hormone receptor-positive metastatic breast cancer and NF1 alterations. It defines PFS as the primary endpoint for Cohort I and describes statistical methods for a planned comparison. These details explain the question the trial was designed to address.

The record does not report PFS results, response results, overall survival results, or interpretable adverse-event results. Therefore, it does not show whether the combination changed the timing of progression or death, whether tumor responses differed, or whether adverse-event incidence differed. It cannot establish that the treatment combination is better, worse, or equivalent to fulvestrant alone. Those conclusions would require comparative outcome data and estimates of their uncertainty.

The trial’s termination after enrollment of 1 participant is important context for interpreting the absence of results. The registry specifically attributes non-reporting to protecting participant privacy and confidentiality. The adverse-event group entries with zero counts should not be interpreted as proof that no events occurred, particularly in light of that explicit privacy statement. No safety comparison can be made from those entries.

The absence of a result does not establish that the planned methods were inappropriate or that a particular clinical outcome occurred. It means the posted record does not provide evidence that can answer the treatment-effect question. The record also does not report why the trial was terminated, its target enrollment, or a sample-size justification. Any explanation for termination or intended precision would therefore be speculation.

In general, a randomized design can support a comparison when enough outcome information is available and when the analysis is conducted as planned. Random allocation alone does not supply that information. For this trial, the registry supports a description of the design and planned analysis, but not a claim about efficacy or safety.

12. Why This Trial Matters Statistically

This trial illustrates why a registered study’s design and its results must be distinguished. The record sets out a clinically focused, biomarker-defined comparison and names an established time-to-event framework for the primary endpoint. But the presence of a detailed endpoint definition and analysis plan does not mean an effect estimate is available. Here, the record reports termination after enrollment of 1 participant and no outcome data, citing privacy and confidentiality.

From a statistical perspective, the small enrollment makes the lack of a comparative estimate especially consequential. Randomization is intended to support a fair comparison between assigned groups, but the registry does not report group assignment or participant outcomes. It is therefore not possible to evaluate treatment balance, event timing, uncertainty, or the assumptions behind the planned analysis. No estimate of treatment effect can be responsibly reconstructed from the information reported.

The case also underscores the role of transparent reporting. The registry provides the primary endpoint definition, planned log-rank test, Cox model, and confidence interval approach, while leaving the actual analysis results unavailable. It lists multiple secondary outcomes but reports no analyses. Readers can identify the planned statistical questions while recognizing that none is answered by the posted results.

Finally, a zero in a registry field is not always evidence of a zero underlying event count. When the record explicitly says that outcomes are not reported for privacy, adverse-event fields should be interpreted cautiously rather than as a clean safety finding. This distinction matters whenever a very small enrollment makes participant confidentiality and statistical interpretability intersect.

13. 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 main limitation is the absence of reported outcome data. The registry states that the study was terminated after enrollment of 1 participant and that no data are reported because the low enrollment number raises participant privacy and confidentiality concerns. There is consequently no usable PFS estimate, treatment contrast, confidence interval, test result, or reported follow-up from which to assess efficacy.

The record does not report the enrolled participant’s characteristics, treatment assignment, treatment received, adherence, progression status, survival status, or length of follow-up. It also does not report the reason for termination. These gaps prevent assessment of whether the intended comparison was implemented or whether any planned endpoint information was collected. The available arm descriptions are incomplete, and the migration eligibility criteria are not reported in full.

The statistical plan is described only in part. The record specifies the primary endpoint and planned tests but does not report detailed censoring rules, analysis populations, missing-data procedures, covariate adjustments beyond treatment, or checks of model assumptions. It does not describe multiplicity handling for the listed secondary outcomes. These are limitations of what can be learned from the registry record; they should not be taken as proof that no further procedures existed.

The adverse-event fields list zero counts across the displayed groups, but the privacy-based non-reporting statement means those entries cannot establish that no events occurred. No safety comparison can be made. The record also does not report a target enrollment or sample-size justification, so the intended precision and statistical feasibility cannot be assessed.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer (A ComboMATCH Treatment Trial) — NCT05554354.
• Registry record last updated 2026-03-03; status last verified 2025-08.
• Results first posted 2026-03-03.
• 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.

17. Record Summary

NCT05554354 is a phase II randomized, unmasked, parallel-group trial sponsored by the National Cancer Institute. It was designed to compare fulvestrant alone with fulvestrant plus binimetinib in hormone receptor-positive metastatic breast cancer with inactivating or inferred inactivating NF1 alterations. The primary endpoint was PFS in Cohort I, defined as time from randomization to progression or death from any cause, whichever happened first, assessed up to 5 years.

The registry reports a start date of 2024-09-13, a primary completion date of 2025-04-04, terminated status, and enrollment of 1 participant. The planned analysis included a one-sided log-rank test with alpha=0.1, a Kaplan-Meier plot, and a Cox-model hazard ratio with a 95% confidence interval. No analyses are reported. The registry says outcome data are not reported to protect participant privacy and confidentiality. Efficacy and safety conclusions cannot be drawn from the posted results.