Phase II Lapatinib Plus Nab-Paclitaxel As First And Second Line Therapy In her2+ MBC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Lapatinib Plus Nab-Paclitaxel As First And Second Line Therapy In her2+ MBC (NCT00709761), a registered phase 2 study. The primary outcome is Overall Tumor Response (OR).

2. Clinical Question

3. Trial Design

This was an open-label, multicenter, single-arm Phase II study sponsored by Novartis Pharmaceuticals. Its registry identifier is NCT00709761, and the record lists enrollment as 60. The study is marked completed. Its start date is 2008-07-02, and its primary completion date is 2011-01-05.

Participants were women with ErbB2-overexpressing metastatic breast cancer and no more than one prior treatment. The stated objective focused on women who had received no chemotherapeutic regimen in the metastatic setting. The registry summary describes a combination regimen: nab-paclitaxel 100 mg/m2 intravenously once weekly for 3 weeks, followed by a rest week in a 4-week cycle, and lapatinib 1000 mg once daily. Treatment was intended to continue until disease progression or withdrawal from the study.

Because there was a single treatment group and no masking, the study does not provide a randomized comparison with another regimen or a control group. The design can describe response and other outcomes among participants receiving the combination, but it cannot isolate the combination's effect relative to an untreated or alternative-treatment group. The registry lists overall tumor response as the primary outcome and overall survival, duration of response, time to response, time to progression, and progression-free survival as secondary outcomes. Numerical results for these efficacy outcomes are not reported in the registry record.

The registry record does not report the protocol's sample-size justification, detailed statistical analysis plan, or allocation procedures beyond identifying the study as single-arm. It also does not report interim analyses. These absences limit what can be concluded about the planned precision or analysis decisions.

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: A safety cohort was designed into the study to include the first 10 participants enrolled. Enrollment was halted after the enrollment of the fifth participant to allow for the safety review. Enrollment was resumed after the review and protocol amended.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: all participants who received at least one dose of investigational product

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 intent-to-treat (ITT) population comprised of all subjects who received at least 1 dose of investigational product.

6. Primary Endpoint

The registry lists the primary outcome as Overall Tumor Response (OR), measured over Start of treatment to disease progression or death or discontinuation from study or at least 28 days after last dose (up to Week 131).

The primary endpoint is overall tumor response, expressed as the percentage of participants experiencing a confirmed complete response or confirmed partial response. The registry defines complete response as disappearance of all lesions, target and/or non-target. It defines partial response as at least a 30% decrease in the sum of the longest dimensions of target lesions relative to the baseline sum, with non-target lesions not increased or absent. The criteria are RECIST 1.0.

Response is a way to describe whether measurable tumors meet prespecified criteria for substantial shrinkage during treatment. Requiring confirmation is intended to distinguish a response that is sustained on assessment from an unconfirmed change. The endpoint is recorded from the start of treatment until disease progression, death, discontinuation from the study, or at least 28 days after the last dose, up to Week 131.

The analysis population is described as the Intent-to-Treat population, defined in the registry as all participants who received at least one dose of investigational product. The registry record does not report the number of participants with a complete or partial response, the overall response percentage, or an uncertainty interval. Therefore, the endpoint definition is available, but the magnitude and precision of the observed response cannot be assessed from the reported efficacy information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical feature is the single-arm design. In a randomized comparison, outcomes in treatment groups can be contrasted under the study's allocation process. In a single-arm study, there is no concurrent control group, so the analysis can describe outcomes among treated participants but cannot directly estimate a between-group treatment difference. General statistical interpretation therefore requires care: a response percentage, even if reported, would be an estimate for the study population under the observed conditions, not a randomized comparison with another therapy.

What does a response percentage represent?

For a binary endpoint such as overall tumor response, each participant is classified according to whether the defined event occurred. The percentage summarizes the share of the analysis population meeting the response definition. Its precision depends on the number of participants and the observed distribution of responses. A confidence interval expresses uncertainty around an estimate, rather than guaranteeing that the underlying value lies within a particular range. The registry record defines the response event but does not report its count, percentage, or confidence interval.

Here, the response event requires a confirmed complete or partial response under RECIST 1.0. The definition sets out the lesion changes that qualify. This prespecification matters because a clearly defined event makes the endpoint more reproducible across assessments. The registry also identifies the evaluation period, from treatment start to disease progression, death, discontinuation, or at least 28 days after the last dose, up to Week 131. The record does not provide participant-level assessment timing or further detail about how unavailable assessments were handled.

Why does the absence of a comparator matter?

Without a control group, outcomes may reflect a mixture of treatment exposure, underlying disease characteristics, prior treatment, follow-up, and other influences. A change observed during treatment is not by itself proof that the combination caused the change. General causal interpretation is stronger when a suitable comparison group helps distinguish treatment effects from other explanations. That comparison is not part of this single-arm design.

The registry's sample-size assumptions describe planning illustrations, not the trial's own design or observed power. Those illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. The study itself is single-arm, so the equal-allocation assumption belongs to the hypothetical planning exercise rather than the trial's treatment allocation. Sample-size illustrations are planning quantities, not evidence that the trial had a particular probability of detecting an effect. The registry record does not report the study's own sample-size justification.

What can be inferred from a missing result?

When an outcome definition is present but its numerical result is absent, no estimate can be recovered from the definition alone. It would be inappropriate to infer the response count from the enrollment, the treatment schedule, or the listed secondary outcomes. The registry record does not report the primary response estimate or its uncertainty. Consequently, statistical precision and compatibility with alternative response values cannot be assessed from this record.

General statistical reporting also benefits from knowing how the analysis population was constructed, how missing assessments were treated, and whether endpoint definitions changed. The registry defines the primary analysis population as participants who received at least one dose of investigational product. Further details on missing-data handling and analysis procedures are not reported in the registry record. The named secondary endpoints likewise do not establish how they were analyzed or whether results were adjusted for multiple testing.

Over-dispersion is a general concern for outcomes whose variability is greater than a statistical model expects. It can make model-based standard errors too small if ignored. That concept does not supply a result for this study: the registry describes the primary endpoint as a percentage and does not report a model, dispersion estimate, or adjusted analysis for it. No conclusion about over-dispersion or model adequacy can be drawn from the registry 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("Lapatinib 1000 mg + Nab-Paclitaxel")
n      <- c(60)
events <- c(32)
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 1000 mg + Nab-Paclitaxel  60  32  53.3  40.0  66.3  40.9  65.4  40.8  65.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists overall tumor response as the primary outcome and identifies overall survival, duration of response, time to response, time to progression, and progression-free survival as secondary outcomes. Considering multiple outcomes can raise a multiplicity question: when many statistical tests are conducted, the chance of at least one apparently notable result may increase. General approaches include prespecifying a primary test or adjusting interpretation for multiple comparisons. The registry record does not report a multiplicity strategy, an ordering of secondary tests, or results that would show how such a strategy was applied.

The record lists 6 outcome measures and 1 analysis, but does not explain the scope of that analysis or provide a detailed statistical analysis plan. It does not report interim analyses. Those details are not reported in the registry record, so it is not possible to determine whether planned testing was limited or whether any adjustment was used.

The primary analysis population is defined as all participants who received at least one dose of investigational product. The registry does not report how missing tumor assessments, treatment discontinuations, or other incomplete outcome data were handled. It also does not report whether the endpoint analysis included all participants in the listed enrollment or whether exclusions occurred. These omissions matter because the treatment of missing outcomes can affect a binary response estimate.

Without a reported response result, missing-data approach, and multiplicity plan, the endpoint's estimate and inferential context cannot be evaluated. These are reporting limitations, not evidence that a particular analysis was or was not performed.

12. Safety Results

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

Deaths

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 (5.0%), dehydration (5.0%), anaemia (3.3%), febrile neutropenia (3.3%), left ventricular dysfunction (3.3%).

The registry lists 60 participants at risk for serious adverse events and reports serious adverse events affecting 21 participants. It lists 3 deaths. These are descriptive safety figures; the registry information does not establish that the serious events or deaths were caused by the study treatment. The record does not provide a comparison group that could contextualize these counts against another treatment.

The listed serious adverse event terms are diarrhoea, 5.0%; dehydration, 5.0%; anaemia, 3.3%; febrile neutropenia, 3.3%; left ventricular dysfunction, 3.3%; and cellulitis, 3.3%. These entries identify selected serious-event terms and their reported percentages. The record does not provide enough detail to determine event timing, duration, recurrence, severity beyond the serious-event classification, or relationship to treatment. The figures should not be read as a complete listing of all adverse events or as evidence of comparative risk.

Safety assessment was planned at 8 and 12 week intervals and at the end of treatment, according to the registry summary. Numerical results for other safety outcomes are not reported in the registry record. The listed counts and percentages therefore provide limited descriptive information rather than a full safety profile.

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

The study's question was whether lapatinib plus nab-paclitaxel showed antitumor activity in women with ErbB2-overexpressing metastatic breast cancer, with no more than one prior treatment. The registry defines a primary measure of activity: the percentage with confirmed complete or partial response according to RECIST 1.0. But it does not report the numerical value of that outcome. The posted efficacy information therefore does not show how many participants responded or how precise a response estimate would be.

The single-arm design is important to interpretation. Even when outcomes are observed after treatment, the absence of a concurrent comparator prevents a direct randomized estimate of the difference between this combination and another approach. The design can describe what happened among participants enrolled in the study; it cannot by itself separate treatment effects from other possible influences on outcomes.

The registry identifies several secondary outcomes, including progression-free survival and overall survival, but does not report their numerical results. Their inclusion in the record should not be mistaken for evidence of a particular outcome. Similarly, the safety figures are descriptive and do not establish treatment causation or comparative safety.

The available information supports statements about the study's design, population, intended treatment, endpoint definitions, and selected serious adverse event figures. It does not support a conclusion that the treatment works or does not work, nor does it support a precise estimate of benefit or harm. Such conclusions would require reported outcome results and sufficient information about their analysis and uncertainty.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and endpoint results must be considered separately. The registry gives a detailed definition of overall tumor response, including what counts as complete or partial response under RECIST 1.0. A precise definition tells readers what the investigators intended to measure, but it cannot substitute for the observed response count, percentage, or uncertainty interval. Those numerical results are not reported in the registry record.

The single-arm design also highlights the difference between describing an outcome and estimating a comparative effect. The study can be framed around activity in a defined population, but without a concurrent comparator it cannot directly establish how outcomes differ from an alternative treatment group. That distinction is central when interpreting Phase II evidence.

The record additionally shows why analysis details matter. The primary analysis population is identified, yet the handling of missing assessments, multiplicity, and detailed statistical procedures is not reported. Such details help readers understand whether an estimate might depend on analysis choices and how much confidence to place in secondary findings.

Finally, sample-size planning illustrations should not be confused with observed statistical power. The registry's stated illustration assumptions concern hypothetical two-arm planning, while the study itself is single-arm. This is a useful reminder that a planning calculation does not establish what the trial demonstrated. In this record, the missing efficacy results prevent assessment of the primary endpoint's magnitude and precision.

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 statistical interpretation is that the registry record does not report the numerical primary endpoint result. It defines overall tumor response and the relevant population, but gives no response count, percentage, or confidence interval. As a result, the primary outcome cannot be quantitatively interpreted from the registry information.

The single-arm, open-label design has no concurrent control group and no masking. It can describe outcomes in participants receiving lapatinib plus nab-paclitaxel, but it does not provide a randomized comparison or directly estimate a treatment contrast. The registry record does not report allocation procedures beyond the single-arm description.

Although secondary efficacy outcomes are named, their numerical results are not reported in the registry record. Details of missing-data handling, the statistical analysis plan, multiplicity control, and interim analyses are also not reported. The record therefore does not permit assessment of how incomplete assessments or multiple outcome analyses were addressed.

Safety reporting is limited to the listed serious adverse event counts and terms. The record does not establish causality, provide a comparison group, or describe all safety outcomes in the information available. The registry's enrollment figure does not, by itself, establish how many participants contributed data to each outcome analysis.

These constraints mean that the study's question and methods can be described, but the efficacy estimate, its precision, and the comparative meaning of the safety figures cannot be fully evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Lapatinib Plus Nab-Paclitaxel As First And Second Line Therapy In her2+ MBC — NCT00709761.
• Registry record last updated 2019-03-26; status last verified 2019-03.
• Results first posted 2011-11-22.
• 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

NCT00709761 is a completed, open-label, multicenter, single-arm Phase II study sponsored by Novartis Pharmaceuticals. The registry record lists enrollment as 60, a start date of 2008-07-02, and a primary completion date of 2011-01-05.

The study evaluated lapatinib plus nab-paclitaxel in women with ErbB2-overexpressing metastatic breast cancer. Overall tumor response was the primary endpoint, defined as confirmed complete or partial response according to RECIST 1.0. Secondary outcomes included overall survival, duration of response, time to response, time to progression, and progression-free survival.

The registry record does not report the numerical primary response result or numerical results for the named secondary efficacy outcomes. It reports serious adverse events affecting 21 of 60 participants at risk and lists 3 deaths, with selected serious-event terms and percentages. These figures are descriptive and do not establish treatment causation.