Lapatinib + Vinorelbine in ErbB2 Overexpressing, First or Second Line Metastatic Breast Cancer Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lapatinib + Vinorelbine in ErbB2 Overexpressing, First or Second Line Metastatic Breast Cancer Subjects (NCT00709618), a non-randomized phase 2 study. The primary outcome is Number of Participants With Overall Response (OR), as Assessed by the Investigator.

2. Clinical Question

3. Trial Design

This was a Phase II, open-label, multi-center, single-arm study. Allocation is recorded as non-randomized, the study model as single-group, and masking as none. These features mean that the registry describes treatment with lapatinib and vinorelbine without a parallel control group or blinded outcome assessment. The design can document responses and adverse events among participants treated in the study, but by itself it does not estimate a randomized treatment contrast.

The study concerned women with ErbB2-overexpressing metastatic breast cancer in either a first- or second-line setting. The summary describes vinorelbine administered intravenously once weekly for 3 weeks, followed by a rest week in a 4-week cycle, with lapatinib taken daily. Treatment was to continue until disease progression or withdrawal from the study. Safety and efficacy assessments were described at 4, 8 and 12 week intervals and at the end of treatment. The primary outcome description specifies investigator assessment every 8 weeks for up to 2 years.

The registry enrollment field reports 44, while the brief summary says that sixty subjects will be enrolled. These are not the same figure or type of statement: the first is the enrollment value recorded in the registry, and the second is the planned enrollment described in the summary. The record does not explain the difference. It lists a start date of 2008-06, primary completion of 2012-05, and status as terminated. The reason for termination is not reported in the registry record.

Secondary outcomes include investigator-assessed progression-free survival, duration of response, time to response, time to progression, and overall survival, as well as counts of participants with specified adverse events related to the combination. The registry record lists these outcomes but does not provide their numerical results in the registry record 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:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: participants who received \>=1 dose of investigational product. To be assigned a status of PR/CR, a confirmatory disease assessment (including bone scan/positron emission tomography scan documenting that progression/ new lesions hasn't occurred) had to be performed \>=4 weeks after response criteria were first met.

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 Number of Participants With Overall Response (OR), as Assessed by the Investigator, measured over From the start of study medication until disease progression, assessed every 8 weeks for up to 2 years.

The primary endpoint is the number of participants with overall response, as assessed by the investigator. Overall response is a binary outcome at the participant level: a participant either meets the response definition or does not. The record defines response as a confirmed complete response or partial response, with best response determined from the start of treatment until disease progression or recurrence. A complete response requires disappearance of all target lesions. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference.

Confirmation matters because an apparent change at one assessment may not establish a response that meets the protocol’s definition. The record says a confirmatory disease assessment, including bone scan or positron emission tomography scan documenting that progression or new lesions had not occurred, was required for a participant to be assigned a complete or partial response. The endpoint was assessed by the investigator every 8 weeks for up to 2 years, according to its stated timeframe.

In general, a response endpoint provides a defined way to summarize tumor changes during a study. It can be useful for describing observed activity in a single-group study, but it does not by itself show what would have happened to comparable participants under a different treatment. The registry record gives the endpoint definition but does not report its observed participant count or a corresponding estimate of precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial’s methods determine what its results can describe. This study is listed as Phase II, single-group, non-randomized, and unmasked. Its primary endpoint is a participant count based on an investigator-assessed response definition. The registry record does not report a statistical analysis plan, a primary result, or an inferential analysis. General statistical explanations below therefore clarify how such methods are ordinarily interpreted; they should not be read as claims about analyses that were actually performed in this study.

What does a single-group design estimate?

A single-group study follows participants receiving the study regimen and records outcomes under that regimen. For a binary endpoint such as overall response, the basic descriptive result would be the number meeting the response definition, together with the number evaluated under the stated analysis population. A response proportion could then be estimated if both the count and denominator were reported. Neither the primary response count nor its analyzed denominator is reported in the registry record, so neither that proportion nor its precision can be stated.

General statistical principle: a confidence interval expresses uncertainty around an estimate under specified assumptions. It does not repair limitations in the design or make an uncontrolled result equivalent to a randomized comparison. The record does not report a confidence interval for the primary endpoint. Nor does it report a hypothesis test or p-value for that endpoint. No statistical significance claim can therefore be made from the information recorded.

Why does randomization matter for a treatment contrast?

Random assignment is a way to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. This study has no separate randomized group, so it cannot estimate a between-group difference from a randomized contrast. Any attempt to compare its outcomes with results from a different population or study would introduce questions about comparability that are not resolved by this record. General statistical principle: a difference between an observed outcome and an external benchmark is not automatically a causal treatment effect.

The study is open-label and has no masking. The primary endpoint is assessed by the investigator. General statistical principle: when outcome assessment is not blinded, knowledge of treatment may influence subjective judgments, although the extent of any influence cannot be determined from the design label alone. The response criteria include defined lesion changes and confirmatory assessment, which specify how response is classified, but the registry record does not describe any additional procedures to limit assessment bias.

How should the response definition be read?

The outcome counts participants whose best response from treatment start until progression or recurrence was a confirmed complete or partial response. Complete response is defined by disappearance of all target lesions; partial response is defined by at least a 30% decrease in the sum of target-lesion longest diameters relative to baseline. The record also defines disease progression using an increase of at least 20% relative to the smallest sum recorded since treatment started, or the appearance of at least one new lesion. These rules classify response using assessments over time rather than a single unqualified observation.

The stated population is the Intent-to-Treat population, defined in the record as participants who received at least one dose of investigational product. The record additionally says that confirmation, including imaging documenting that progression or new lesions had not occurred, was required to assign complete or partial response. It does not give a separate rule for participants without an evaluable follow-up assessment, nor does it report how missing assessments were handled. That uncertainty matters because a response count depends on both outcome classification and the handling of participants whose status cannot be determined.

What can safety counts and planning calculations tell us?

The safety fields report counts of participants affected and at risk. Such counts describe how many participants were recorded with at least one event under the relevant safety category; they do not state the number of event episodes or the duration each participant was observed. General statistical principle: event counts can be affected by follow-up time, event definitions, and the approach to coding events. The registry record does not supply enough detail to infer those features beyond its stated categories and terms.

The record notes that sample-size illustrations are planning calculations based on an observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. These are described as illustrations rather than the trial’s own design. They do not establish that the study had a particular power, and a planning calculation is not observed power. The record does not provide numerical outputs for those illustrations in the registry record for this analysis, and the single-group design itself is not a two-arm randomized comparison. General statistical principle: planning assumptions are hypothetical inputs for a future design, not evidence that an effect has been established.

Overall, the methods support a clear reading of the endpoint definition and study structure, but key information for evaluating the primary result is absent. The registry record does not report a response count, an analysis denominator, a confidence interval, a p-value, or the detailed statistical plan. Without those, it is not possible to assess the numerical magnitude or statistical precision of the primary endpoint from the record.

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("Vinorelbine 20 mg/m^2 Plus Lapatinib 1500 mg")
n      <- c(44)
events <- c(18)
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  Vinorelbine 20 mg/m^2 Plus Lapatinib 1500 mg  44  18  40.9  26.3  56.8  27.7  55.6  27.7  55.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and several secondary outcomes: investigator-assessed progression-free survival, duration of response, time to response, time to progression, overall survival, and specified adverse events. It does not report how hypotheses across these outcomes were prioritized or whether any adjustment for multiple comparisons was planned or performed. When many outcomes are examined, general statistical principle: the chance of at least one apparently notable result can increase if each is treated as an independent confirmatory test without an appropriate strategy. The record does not establish that these outcomes were tested in that way, so no claim about multiplicity-adjusted inference can be made.

The primary outcome population is defined as participants who received at least one dose of investigational product. This is the registry’s stated Intent-to-Treat definition; it should not be assumed to match other common uses of that term. The record does not report the number included in the primary analysis, whether all treated participants had an evaluable response assessment, or how participants with missing follow-up were classified. It also does not describe imputation, censoring, or other missing-data procedures. These details are important because the interpretation of a response count depends on how unknown outcomes are handled.

The registry record does state that a confirmatory assessment was required for complete or partial response, and it describes the assessment schedule. This clarifies part of the endpoint classification process but does not specify what happened when a scheduled assessment was unavailable or when confirmation could not be obtained. The reason for study termination is not reported. The record also does not report an analysis plan or numerical results for the listed secondary outcomes. Consequently, multiplicity, missing-data handling, and the exact analysis populations beyond the stated primary population cannot be evaluated from this 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: neutropenia (34.1%), febrile neutropenia (6.8%), diarrhoea (6.8%), abdominal pain (4.5%), dehydration (4.5%).

The registry reports 22 participants affected among 44 at risk for serious adverse events. For other adverse events, it reports 44 participants affected among 44 at risk. These are participant counts in the listed safety categories; they are not counts of individual event episodes, and the record does not state how many episodes each participant experienced.

The serious adverse event terms listed with percentages are neutropenia, 34.1%; febrile neutropenia, 6.8%; diarrhoea, 6.8%; abdominal pain, 4.5%; dehydration, 4.5%; and gastritis, 2.3%. These percentages are reported as term-specific figures in the registry record. They should not be added together: participants may have experienced more than one event, and a combined total cannot be inferred from these entries.

The study has no control group, so these safety findings describe events recorded during treatment in the study, not the amount of risk attributable to the combination relative to another treatment. The record does not provide event timing, exposure duration for each participant, or comparative safety estimates. The listed event counts and percentages should therefore be read descriptively, with the limits of the single-group design in mind.

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

The record shows how the investigators defined and planned to assess overall response in a Phase II study of lapatinib plus vinorelbine. It also reports selected safety counts and serious adverse event terms. These are useful pieces of information about the study’s endpoint and recorded safety experience. However, the registry record does not report the number of participants with overall response, so the primary efficacy finding cannot be described numerically from this record.

The absence of that result should not be interpreted as a zero response count or as proof of a particular clinical conclusion. It means only that the primary count is not reported in the registry record. Without the response count and an analysis denominator, there is no basis for calculating a response proportion or judging its precision. The record also does not report a confidence interval or statistical test for the primary outcome.

The single-arm, non-randomized design means that outcomes observed among treated participants do not provide a randomized comparison with another treatment or with no study treatment. General statistical principle: an observed outcome can describe what happened in a study group, but a causal comparison requires a credible counterfactual, commonly supported by randomization. This design does not supply that comparison. The record therefore cannot establish how the combination compares with an alternative regimen.

The safety counts describe reported events in the study and should not be treated as comparative risks. The listed serious event percentages are not a complete account of all safety questions, and the record does not state event duration or provide a control group for context. The terminated status also does not explain why the study ended; the reason is not reported in the registry record. These limitations do not erase the descriptive information, but they constrain what can be concluded from it.

In short, the registry record supports an account of study design, response criteria, and selected adverse event information. It does not provide the primary response result or the comparative and inferential information needed to quantify a treatment effect. Any interpretation should keep those distinctions clear.

14. Why This Trial Matters Statistically

This study illustrates why design details and outcome reporting matter alongside an endpoint’s definition. The response criteria are specified, including the requirement for confirmation and the timing of investigator assessments. Those details make the intended classification more transparent. Yet the absence of the primary response count prevents readers from seeing the central outcome in numerical form. A well-defined endpoint and a reported endpoint result answer different questions.

The single-group design also makes the inferential boundary visible. The study can describe responses and adverse events among participants who received the combination, but it does not include a randomized comparator. That distinction is important when interpreting an observed outcome: description of an outcome in a treated group is not the same as an estimate of how treatment changes outcomes relative to an alternative.

The registry record further illustrates why analysis populations and missing-data rules matter. It defines the primary population as participants who received at least one dose, but does not report the primary analysis denominator or how missing assessments were handled. Without these details and the response count, the precision and completeness of the primary result cannot be assessed. The separate enrollment statements, 44 in the enrollment field and sixty planned in the summary, also demonstrate the value of distinguishing a registry enrollment value from a planned target.

Finally, safety findings require context. The record identifies serious adverse events and their reported percentages, but the single-group design does not provide a comparison for estimating relative risk. Statistical interpretation depends not only on a list of numerical values, but also on the design, population, outcome rules, and completeness of reporting. This study is therefore a useful example of how those elements shape what can be learned from a clinical trial record.

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 main limitation for interpreting efficacy is that the registry record does not report the number of participants with the primary outcome. It also does not report the denominator used for that analysis, a confidence interval, or a hypothesis test. As a result, the primary response estimate and its precision cannot be assessed from the record. The endpoint definition is detailed, but the numerical result needed to apply that definition is absent.

The non-randomized, single-group design has no concurrent control group. Outcomes in the treated group therefore cannot establish a comparative treatment effect. The study is open-label, and response was assessed by the investigator; the record does not describe further measures to address possible assessment bias. The response criteria and required confirmation provide classification rules, but they do not overcome the absence of blinding or a comparator.

The record reports an enrollment value of 44, while its brief summary says sixty subjects would be enrolled. It does not explain the difference or state how many participants contributed to each outcome analysis. The reason for termination is also not reported. The record does not describe missing-data handling, the detailed statistical analysis plan, or any multiplicity strategy for the several listed outcomes. These omissions limit assessment of analysis choices and the robustness of reported findings.

For safety, the record gives participant counts and selected serious adverse event terms, but not event episodes, timing, or a comparison group. It does not permit a comparative assessment of safety. The available information is therefore descriptive and incomplete for judging either the primary efficacy result or relative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lapatinib + Vinorelbine in ErbB2 Overexpressing, First or Second Line Metastatic Breast Cancer Subjects — NCT00709618.
• Registry record last updated 2014-07-14; status last verified 2014-06.
• Results first posted 2013-01-18.
• 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

NCT00709618 is a Phase II, open-label, multi-center, non-randomized, single-group study of lapatinib plus vinorelbine in women with ErbB2-overexpressing metastatic breast cancer in a first- or second-line setting. The primary outcome is investigator-assessed overall response, defined by confirmed complete or partial response. The enrollment field reports 44; the brief summary describes a plan to enroll sixty subjects. The record lists status as terminated, with no reason reported.

The registry reports 22 participants affected among 44 at risk for serious adverse events and 44 affected among 44 at risk for other adverse events, along with selected serious event terms and percentages. The primary response count, its analysis denominator, and detailed inferential results are not reported in the registry record. The single-group design supports descriptive interpretation but does not provide a randomized treatment comparison.