Lapatinib Ditosylate and Radiation Therapy in Treating Patients With Locally Advanced or Locally Recurrent Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lapatinib Ditosylate and Radiation Therapy in Treating Patients With Locally Advanced or Locally Recurrent Breast Cancer (NCT01868503), a na phase 2 study. The primary outcome is Percentage of Patients Achieving Complete Clinical Response.

2. Clinical Question

Statistically, the central question is descriptive: how many participants met the specified clinical-response definition during the stated assessment period? The registry record does not report an observed response count or percentage, nor does it provide a comparison group from which to estimate a treatment contrast. The study also listed questions about feasibility of biomarker assessment, change in the proportion of breast cancer stem cells, adverse events and pathologic complete response for participants undergoing surgery. Those outcomes address distinct aspects of treatment and measurement; none should be treated as a substitute for the primary clinical-response endpoint.

3. Trial Design

This was a Phase II, single-group study sponsored by Stanford University. The registry record lists allocation as not applicable and masking as none. With no concurrent control group, the design can describe outcomes observed during the study, but it cannot by itself distinguish effects associated with the treatment from changes that might have occurred for other reasons. The record lists 7 enrolled participants and gives the status as terminated.

The study concerned concurrent lapatinib ditosylate and radiation therapy in locally advanced or locally recurrent breast cancer. According to the arm description, participants received lapatinib by mouth once daily beginning on day 1, continuing until completion of radiation therapy. Radiation therapy began on day 7 and was planned for 5-7 weeks. Blood banking for laboratory biomarker analysis was also described. These are the planned treatment details in the registry record; they do not establish which treatments were actually received or completed by each participant.

The listed study dates are a start in 2013-07 and primary completion in 2014-12. The termination status is important when interpreting the record: it describes a study that did not proceed as an ongoing trial, but the reason for termination is not reported in the registry record. A protocol-level explanation of how termination affected recruitment, follow-up or endpoint assessment is also not reported in the registry record.

The registry lists five outcome measures. The primary measure is the percentage of patients achieving complete clinical response, with a timeframe of up to 12 weeks. Secondary outcomes cover feasibility of assessing breast cancer stem cells using flow cytometry and SCGEP, change in the proportion of those cells, adverse events graded under CTCAE Version 4.0, and pathologic complete response among participants undergoing surgical resection. The record does not report results for these outcomes in the information available for this analysis.

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:

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 Percentage of Patients Achieving Complete Clinical Response, measured over Up to 12 weeks.

The primary endpoint is titled “Percentage of Patients Achieving Complete Clinical Response.” It is intended to capture whether a participant had no tumor on the chest wall, in the treated breast or in the nodal regions. Assessment was defined by clinical examination, with radiographic imaging if clinically indicated, and the timeframe is up to 12 weeks. This endpoint focuses on a clinical assessment of disease after the combined treatment rather than on a laboratory marker alone.

A response endpoint can provide a direct summary of how many participants met a prespecified clinical definition. Its usefulness depends on applying that definition consistently and having sufficiently complete assessments at the stated time. The endpoint title refers to a percentage, while the registry’s structured measure describes a count of participants. The record does not report an observed count, percentage, denominator for the endpoint analysis, or details about how assessments at different times within the timeframe were handled.

The endpoint is not a comparison of treatments: the study has one group and no control arm. The registry record also does not report the primary endpoint result. Consequently, the definition clarifies what was intended to be measured, but the record does not establish how many participants met that definition or how precisely any response rate was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group clinical study records outcomes among participants receiving the study treatment. A proportion or count can describe what occurred in that group, provided the outcome definition, assessment process and analysis population are clear. The design does not create a concurrent estimate of what would have happened under an alternative treatment. As a result, it cannot isolate the effect of the intervention from other influences on the observed outcome.

For this study, the registry lists a single treatment group combining lapatinib ditosylate and radiation therapy, with allocation marked not applicable. It describes no randomized control group. The primary clinical-response endpoint could have been reported descriptively, but the registry record does not report a result. Even a complete descriptive result would not constitute a randomized treatment contrast.

How should the clinical-response endpoint be understood?

The primary endpoint is described as a percentage, while the structured measure is a count of participants. These are related ways of presenting a binary outcome: each participant either meets the complete-response definition or does not, and a count can be related to a proportion if the relevant denominator is known. The record does not report the endpoint count, the analysis denominator or the resulting percentage. No rate should be inferred from enrollment alone, because enrollment does not establish that every participant received treatment, had an evaluable assessment or was included in the endpoint analysis.

The endpoint specifies absence of tumor at the chest wall, treated breast and nodal regions, assessed by clinical examination with radiographic imaging if clinically indicated. The registry gives a timeframe of up to 12 weeks but does not report the assessment schedule, rules for handling assessments at different times, or criteria for classifying unevaluable participants. Those details can affect how consistently a response endpoint is measured.

What does precision mean for a response estimate?

In general, a confidence interval describes the uncertainty around an estimate under a stated statistical model. A narrow interval indicates greater precision under that model; a wide interval indicates less precision. For a binary endpoint, the amount of information depends on the number of participants with assessable outcomes and on how the outcomes are distributed. A small study will generally provide limited precision, particularly when few outcome events or responses are observed.

No confidence interval or other uncertainty measure for the primary endpoint is reported in the registry record. It is therefore not possible to assess the precision of a response estimate from the posted primary outcome information. No interval should be reconstructed without an observed result and a defined analysis population.

What do the planning assumptions mean?

General power calculations ask how often a specified statistical procedure would detect a specified effect under assumptions about the design and data. They are planning tools, not a description of what a completed study demonstrated. The planning assumptions recorded for the related illustrations are a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are not the registered design of this trial, which is single-group, and they should not be interpreted as observed power.

Planning illustrations based on an effect are conditional on that effect and on their assumptions. They do not show that the effect is real, that a future trial will achieve its target, or that this study had adequate power. The registry record does not report its own sample-size justification or statistical plan. No sample-size illustration can replace a reported primary endpoint estimate and its uncertainty.

How should the safety counts be read?

In general, a count of participants affected is different from a count of events: one participant may experience more than one event, depending on the reporting convention. A denominator indicates the group considered at risk or assessed, while the affected count describes participants recorded with an event. The registry’s safety entries list participants at risk and affected for serious and other adverse events. They are not comparisons against a separate group.

Seriousness and severity are also distinct concepts in general safety reporting. The record says adverse events were to be graded according to CTCAE Version 4.0 as a secondary outcome, but the posted serious-event summary does not provide event grades in the registry record for this analysis. Nor does it describe event duration, timing, attribution to treatment or whether individual participants experienced multiple listed terms. These details should not be assumed from the counts or terms alone.

What can be inferred from the posted analysis information?

The registry lists no analysis records. That means no statistical result, adjustment method, uncertainty interval or analysis population can be evaluated from those records. It does not establish that no analyses were conducted outside the registry record. Whether outcome assessors were blinded, how missing data were handled, and whether planned analyses were changed are not reported in the registry record. The distinction between what the trial may have done and what the record reports is essential when describing the available evidence.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lapatinib Plus Radiation Therapy")
n      <- c(7)
events <- c(2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lapatinib Plus Radiation Therapy  7  2  28.6  3.7  71.0  8.2  64.1  8.5  65.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures: a primary clinical-response endpoint and secondary measures concerning biomarker feasibility, change in the proportion of breast cancer stem cells, adverse events and pathologic complete response among participants undergoing surgical resection. Multiple outcomes can answer different questions, but testing many hypotheses can increase the chance of at least one apparently notable result arising by chance. In general, researchers may address this through prespecified priorities, adjustment procedures or cautious interpretation. The registry record does not report a multiplicity strategy, such as a hierarchy among secondary outcomes or an adjustment for multiple testing.

The record lists no analysis records and does not report results for the primary or secondary outcomes in the information available for this analysis. It therefore does not provide p-values, confidence intervals, model specifications or enough detail to assess whether analyses were prespecified. The statistical analysis plan is not reported in the registry record.

Missing-data handling and analysis populations are also not reported in the registry record. The record does not say how many participants completed treatment, had outcome assessments, were included in an endpoint analysis or had incomplete follow-up. Enrollment is not necessarily the same as the number analyzed. There is no reported description of an intention-to-treat, per-protocol or safety population, and no account of how missing or unevaluable outcomes were classified.

These omissions limit both interpretation and reproducibility. In general, excluding participants with missing assessments can change an estimated response proportion if missingness is related to outcomes or treatment experience. A clear analysis population and missing-data approach help readers understand whom a result represents. Since no primary endpoint result or analysis method is reported, neither the direction nor the possible impact of missing data can be assessed from the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lymphocyte count decreased (14.3%), anemia (14.3%), fever-possible sepsis (14.3%), chest pain (14.3%).

The safety record lists 7 participants at risk for serious adverse events and 3 affected in the combined lapatinib ditosylate and radiation therapy group. For other adverse events, it lists 7 at risk and 1 affected. These are registry counts for this group, not treatment-versus-control comparisons. The listed serious adverse-event terms are lymphocyte count decreased, anemia, fever-possible sepsis and chest pain, each reported at 14.3%.

The percentages are reproduced as listed; the record does not explain the event-level calculation or whether participants could contribute to more than one term. The counts should not be treated as a complete account of all adverse events, their timing, duration, severity or relationship to treatment. Although the secondary outcome description says adverse events were graded according to CTCAE Version 4.0, grade details for these listed serious terms are not reported in the registry record.

The deaths field is null. That is a missing entry, not a reported count of zero deaths. The registry record does not report the reason for the missing value or further safety follow-up information. These safety figures should therefore be read as limited descriptive entries rather than a comprehensive estimate of risk.

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

The record establishes that a Phase II, single-group study of lapatinib ditosylate with radiation therapy was registered, lists 7 participants as enrolled, and gives the study status as terminated. It also specifies a clinical-response definition and reports a limited set of safety counts and serious adverse-event terms. These details characterize the registered study and what is posted, but they do not establish a clinical treatment effect.

The primary endpoint result is not reported in the registry record. There is no posted response count, percentage, denominator for endpoint analysis or precision estimate. It is therefore not possible to say from this record how often complete clinical response occurred or how uncertain an estimate would be. The outcome definition alone is not evidence that participants achieved a response.

Nor does the single-group design support a treatment comparison. Without a control group, any observed outcome would not reveal what would have happened to comparable participants under another approach. The record does not support a claim that the treatment combination works or does not work. The posted safety counts also cannot establish comparative safety, and the missing death entry cannot be interpreted as zero deaths.

More broadly, the registry record does not report why the study was terminated, whether all intended assessments were completed, or how missing data were addressed. No statistical analysis results or analysis populations are reported. These gaps make it especially important to distinguish the study’s intended questions from findings that are actually documented. The defensible interpretation is that the trial was designed to assess clinical response and several secondary outcomes, but the posted record does not provide enough outcome analysis to answer those questions.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between a registered endpoint and a reported result. The primary response definition is specific about the clinical locations assessed and allows radiographic imaging when indicated. Yet a well-described endpoint does not answer the research question unless the record also reports the observed outcome, the population analyzed and some indication of precision.

The single-group design also makes the target of inference important. A descriptive response proportion, if reported, would characterize participants in the study; it would not be a randomized estimate of how the treatment compares with an alternative. That distinction is fundamental when translating a clinical outcome into a claim about treatment effects. A study can address feasibility or provide early descriptive information without resolving comparative effectiveness.

The record’s termination status and limited analysis information illustrate why registry results need to be interpreted with care. The reason for termination, outcome completion, missingness and analysis populations are not reported in the registry record. Without these details, readers cannot tell how the enrolled group relates to the participants with evaluable outcomes or whether the available results reflect the original analysis plan.

The safety entries likewise show the value of separating counts, denominators and event terms. They offer some descriptive information but lack the detail needed for a complete assessment of event timing, grading or treatment attribution. Overall, the statistical importance of this record lies in clarifying what was planned and what remains undocumented, rather than in offering a quantitative estimate of clinical benefit.

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 most consequential limitation is that the registry record does not report the primary endpoint result or any analysis records. Without an observed count or percentage, an analysis denominator or uncertainty interval, the intended clinical-response question cannot be answered from the posted results. Enrollment alone is not an endpoint analysis population.

The study is single-group, with allocation listed as not applicable and no masking. There is no concurrent control group for a like-for-like comparison. Thus, even a reported outcome would be descriptive and could not by itself establish that the treatment combination caused the outcome. The record does not report details of outcome-assessor blinding or other steps used to limit assessment bias.

The status is terminated, but the reason and any effect on recruitment, treatment delivery, follow-up or data collection are not reported in the registry record. The record does not say how many participants completed treatment or had evaluable assessments. Missing-data methods and analysis populations are also not reported, limiting assessment of possible bias from incomplete information.

For safety, the registry provides counts and selected serious adverse-event terms, but it does not report event timing, duration, grade details for the listed terms, attribution or whether terms overlapped within participants. The deaths field is null, and the record does not clarify that entry. The statistical analysis plan, multiplicity approach and sample-size justification are not reported in the registry record. These limitations restrict what can be concluded from both the efficacy-related and safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lapatinib Ditosylate and Radiation Therapy in Treating Patients With Locally Advanced or Locally Recurrent Breast Cancer — NCT01868503.
• Registry record last updated 2017-06-26; status last verified 2017-06.
• Results first posted 2017-01-19.
• 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

NCT01868503 is a Phase II study sponsored by Stanford University of lapatinib ditosylate with radiation therapy for locally advanced or locally recurrent breast cancer. It used a single-group design, with allocation listed as not applicable and masking as none. The registry lists 7 enrolled participants, a start in 2013-07, primary completion in 2014-12 and status as terminated.

The primary endpoint was the percentage achieving complete clinical response up to 12 weeks, defined by absence of tumor at specified sites on examination, with imaging if indicated. Secondary outcomes concerned biomarker feasibility and change, adverse events, and pathologic complete response among participants undergoing surgery. The record lists no analysis records and reports no primary endpoint result. Safety entries list serious and other adverse-event counts, but the deaths field is null. The reason for termination, analysis populations, missing-data methods and statistical plan are not reported in the registry record.