A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation (NCT01572727), a randomized phase 2, phase 3 study. The primary outcome is Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, placebo-controlled phase II/III study sponsored by Novartis Pharmaceuticals. The registry record describes quadruple masking and an enrollment of 416. The study status is completed. Its start is recorded as 2012-08 and primary completion as 2015-06. These registry dates describe the study record; they do not specify when each participant entered or completed follow-up.

The study compared BKM120 plus paclitaxel with matching placebo plus paclitaxel in adult females with HER2-negative, inoperable, locally advanced or metastatic breast cancer. The brief summary describes daily BKM120 and weekly paclitaxel. The arms are also described as receiving study drug plus paclitaxel or placebo plus paclitaxel. The safety group titles give doses of buparlisib (BKM120) 100 mg and paclitaxel 80 mg per m2, and placebo 100 mg and paclitaxel 80 mg per m2. The record does not give further treatment-delivery or dose-modification details.

The primary outcome description identifies a full analysis set of all participants randomized to study treatment, analyzed according to treatment and strata under the intention-to-treat principle. It states that this was the primary population for efficacy endpoints at interim. It also reports that 338 participants were randomized in a 1:1 ratio between 16-Aug-2012 and 07-Jun-2014. The connection between this efficacy-analysis population and the registry enrollment of 416 is not reported in the registry record. Reasons for any difference, if applicable, are not reported.

The registry lists phase II and phase III components, but the relationship between the phases, including any transition criteria or phase-specific design details, is not reported in the registry record. The record includes an interim reference in the population description and a timeframe tied to futility analysis, but does not report the interim-analysis plan, its decision rules, or the details of any futility assessment. The original sample-size justification and other design assumptions 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.

Before assignment: A total of approximately 524 patients were to be randomized in a 1:1 ratio to one of the two treatment arms irrespective of the adaptation decision to continue in the full or PI3K pathway activated subpopulation. Randomization was stratified by PI3K activation and Hormone Receptor status.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS per Expert Report: All pts randomized to study treatment. Per ITT principle, pts were analyzed according to treatment \& strata. FAS was primary population for analysis of efficacy endpoints at interim. 338 pts were randomized (between 16-Aug-2012 \& 07-Jun-2014) in 1:1 ratio to buparlisib + paclitaxel arm N=168 or placebo + paclitaxel arm N=170.

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 Full Analysis Set (FAS) included all patients who were randomized to study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll), measured over Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed.

Progression-free survival is the time from randomization to the first of radiologically documented disease progression or death from any cause. The registry specifies assessment by the local investigator and defines progression using RECIST v1.1: a 20% increase in the sum of the longest diameters of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. The recorded assessment schedule was every 8 weeks from randomization, until progression, with the stated timeframe extending up to 10 months after futility was analyzed.

This endpoint combines disease progression and death into a time-to-event measure. It therefore concerns how long participants remained alive without documented progression, rather than only whether a response occurred at a particular assessment. The registry reports the median in months for each arm and a hazard ratio for the between-arm comparison. These are different summaries: a median gives the time by which half of the relevant event-time distribution has reached an event, while a hazard ratio compares event rates over follow-up under the assumptions of the chosen time-to-event analysis. The analysis method and its assumptions are not reported in the registry record.

Progression-free survival is used in trials because it captures disease progression as well as death, and because it preserves information about event timing. It is not interchangeable with overall survival, response rate, or duration of response. The registry lists other outcomes, including overall survival, but the primary question analyzed in this result is the local investigator assessment of progression-free survival.

7. Results Posted in the Registry

• BKM120 and Paclitaxel vs Placebo and Paclitaxel: hazard ratio 1.18 (95% CI 0.82–1.68) (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Overall Response Rate (Phase ll)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • BKM120 and Paclitaxel: 22.6% (38/168) versus 27.1% (46/170) on control; risk difference -4.4 percentage points (95% CI -13.6 to 4.8), risk ratio 0.84 (0.58–1.21); unadjusted two-proportion z-test p = 0.345.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between BKM120 and Paclitaxel and the control. The interval gives the range of effects that remain compatible with the data.

Clinical Benefit Rate (CBR) (Phase ll)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • BKM120 and Paclitaxel: 26.2% (44/168) versus 32.9% (56/170) on control; risk difference -6.8 percentage points (95% CI -16.5 to 3.0), risk ratio 0.80 (0.57–1.11); unadjusted two-proportion z-test p = 0.174.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between BKM120 and Paclitaxel and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists several secondary outcomes, including overall survival, overall response rate, duration of response, time to response, clinical benefit rate, pharmacokinetic profiles, and time to definitive deterioration of ECOG performance status. Numeric results are available for overall response rate and clinical benefit rate in the posted outcome information. Numeric results for the other listed secondary outcomes are not reported in the registry record.

Across the two secondary outcomes with numeric results, the arm-level percentages are lower in the BKM120 plus paclitaxel group than in the placebo plus paclitaxel group. The unadjusted recalculated risk-difference intervals include no difference. This direction does not establish that the groups differ, and these outcomes do not offer a more precise resolution of the primary progression-free survival result. The secondary findings are broadly compatible with uncertainty in the primary comparison rather than providing an independent confirmation of a specific effect.

Secondary outcomes are useful because they describe other aspects of the trial, but interpreting many outcomes increases the chance that some apparent differences arise by chance. The registry does not report a multiplicity strategy or identify a hierarchy for testing secondary endpoints. The recalculated p-values are unadjusted and therefore carry less weight than a prespecified, multiplicity-controlled confirmatory analysis would. The endpoint descriptions also vary in their measurement and timing, so they should not be combined into a single claim.

The record does not report whether all listed outcomes were analyzed, whether some results were omitted, or whether any outcome definitions changed. Consequently, the available secondary results should be treated as limited, descriptive evidence. They do not replace the primary endpoint, and the unreported secondary results cannot be inferred from the outcomes that are posted.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Overall Survival by Kaplan-Meier Estimate (Phase ll)
• Overall Response Rate (Phase ll)
• Duration of Response (Phase Lll)
• Time to Response (Phase Lll)
• Clinical Benefit Rate (CBR) (Phase ll)
• Plasma Concentration-time Profiles of BKM120 - Pharmacokinetics (PK) (Phase Lll)
• Time to Definitive Deterioration of ECOG Performance Status (Phase Lll)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is time-to-event data. Each participant contributes information about the time from randomization until progression or death, or until the participant’s observed follow-up ends without either event. In general, time-to-event methods are useful because they retain information about when events occur and can accommodate follow-up that differs across participants. This general explanation does not establish which specific model or censoring rules were used in this trial; those methods are not reported in the registry record.

What the hazard ratio describes

A hazard is the instantaneous event rate among participants who have not yet experienced the event, considered over follow-up. A hazard ratio compares that rate between the assigned groups. A hazard ratio near the no-difference value is consistent with similar hazards under the analysis model; values on either side indicate different relative directions. The registry reports the hazard ratio as 1.18, with a 95% confidence interval from 0.82 to 1.68. The interval covers values on both sides of no difference, so the point estimate alone should not be read as a settled conclusion.

A hazard ratio is not a ratio of the reported medians, nor is it a difference in months. It summarizes a relative event-rate comparison over time, subject to assumptions of the analysis. A common assumption in some time-to-event models is that the relative hazard remains sufficiently stable over follow-up. Whether such an assumption was used or checked is not reported in the registry record. The reported statistic is identified as a hazard ratio, but the analysis method field is not populated.

What the medians add

The arm-specific medians offer an interpretable description of event timing. The reported median is 8.0 months for BKM120 plus paclitaxel and 9.2 months for placebo plus paclitaxel. Each has its own 95% confidence interval. These summaries do not show the full survival curves, the distribution of event times, or the number of participants still under observation at different follow-up times. Those details are not reported in the registry record. The median comparison should therefore be read alongside, rather than substituted for, the reported hazard ratio.

What a confidence interval means

In general, a confidence interval describes the uncertainty around an estimate under the statistical procedure used. A wider interval indicates less precision than a narrower interval on the same scale. The primary hazard-ratio interval, from 0.82 to 1.68, includes values indicating different possible relative hazards. It does not identify a single value as the true effect, and it does not assign a probability to the true value lying inside that particular interval. The registry does not provide enough methodological detail to assess the interval procedure beyond its stated 95% level.

Secondary binary outcomes

Overall response rate and clinical benefit rate are reported as percentages by arm. The additional risk-difference estimates are unadjusted recalculations from posted summary counts. A risk difference expresses the contrast between the two proportions on an absolute scale. Its confidence interval describes uncertainty around that contrast. For both outcomes, the recalculated intervals include no difference. The unadjusted p-values are 0.345 for overall response rate and 0.174 for clinical benefit rate. They are not reported as sponsor analyses, and there is no adjustment for the fact that several outcomes are being considered.

For general context, a p-value measures how incompatible the observed data are with a specified null model, conditional on that model and its assumptions. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. These recalculated p-values do not account for multiplicity and should be interpreted as exploratory descriptions of the posted summaries.

Over-dispersion and modeling

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. In count or clustered data, ignoring over-dispersion can make uncertainty estimates too small and evidence appear stronger than warranted. The primary endpoint is time-to-event, and the registry does not report an over-dispersion assessment or enough modeling detail to determine whether any such issue was relevant. No conclusion about over-dispersion can be drawn from the posted result alone.

Similarly, the record does not report a statistical analysis plan, adjustment factors for the primary comparison, a method for handling deviations from assigned treatment, or diagnostics for model assumptions. The population text says participants were analyzed according to treatment and strata under the intention-to-treat principle. That statement describes the analysis population and grouping, but does not supply the full model specification. Interpretations should remain limited to the posted estimates and their stated intervals.

11. Confidence Intervals and Precision

Precision refers to how tightly an estimate is determined by the observed data and the analysis. The primary arm-specific median estimates have 95% confidence intervals of 7.2 to 9.2 months for BKM120 plus paclitaxel and 7.3 to 11.0 months for placebo plus paclitaxel. These intervals indicate uncertainty in the estimated medians; they are not ranges containing every participant’s progression-free survival time.

The comparative hazard-ratio estimate is 1.18, and its 95% confidence interval extends from 0.82 to 1.68. This interval is broad enough to include a range of possible relative hazards, on both sides of no difference. Thus the reported point estimate is more specific than the data’s precision supports when read alone. The interval is the more informative guide to how uncertain the comparative estimate is. A confidence interval does not guarantee that the true value lies within its limits, nor does it directly state the probability of benefit or harm.

The secondary outcome intervals also communicate uncertainty. The arm-specific overall response rate and clinical benefit rate estimates each have posted 95% confidence intervals, and the recalculated risk-difference intervals include no difference. These findings are not a substitute for the primary endpoint and were not adjusted for multiple testing.

The registry does not provide event counts for the primary outcome, follow-up distributions, numbers at risk over time, or the details of the interval calculation. Those omissions limit independent assessment of how precision changes over follow-up and how much information contributed to the primary estimate. The posted intervals remain the appropriate basis for describing the reported uncertainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial’s original sample-size justification. The assumptions stated for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to be detected is set to the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

For the time-to-event outcome, the planning figures are total event counts, not participants per arm. The listed values are total events needed for 80% power or 90% power under each stated effect-size scenario. For the binary outcomes, the figures are participants per arm. The 80% power column represents the planning number per arm associated with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and model assumptions apply. The 90% power column gives the corresponding planning number for a higher chance of detection. These are design illustrations, not guarantees about what a future study would observe.

The effect scenarios are labeled as planning for 100%, 75%, or 50% of the observed effect. The smaller the effect targeted for detection, the more participants or events are generally needed to distinguish it from random variation at the chosen significance level. That is why the planning figures increase as the assumed effect becomes smaller. The associated curve should be read as a visual representation of that relationship, not as a separate result from the trial.

This is not observed power. Observed power calculated after a trial using its estimated effect does not provide an independent measure of the strength of the evidence; the confidence intervals and estimates are more useful for understanding uncertainty. The illustrations also do not establish that the completed trial was adequately powered for its actual effect, because the original design assumptions are not reported.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.180, so ln(HR) = 0.1655.
2. d = 4 × (1.96 + 0.842)² / [ln(1.180)]² = 1,146.0, rounded up to 1,147 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.18                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(1572727)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 1,147 (80% power), 1,535 (90% power)
 75% of observed effect: events = 2,038 (80% power), 2,728 (90% power)
 50% of observed effect: events = 4,585 (80% power), 6,137 (90% power)
Simulated power with 1,147 events: 0.798 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The primary comparison is reported in the registry as a hazard ratio of 1.18, with a 95% confidence interval from 0.82 to 1.68. This is the sponsor’s reported primary comparative result. There is no sponsor-reported p-value in the registry record. No separate recalculation of the primary hazard ratio is presented, and the record does not identify the method used to calculate it.

For overall response rate and clinical benefit rate, the posted arm-level counts permit simple unadjusted recalculations of risk differences and related statistics. The recalculated results are not sponsor-reported analyses: the record’s reported-analyses lists for those outcomes are empty. The associated unadjusted p-values are 0.345 and 0.174, respectively. They should not be conflated with the primary hazard-ratio analysis, which uses a time-to-event measure and is reported directly in the registry.

The registry indicates no discrepancy between the comparison and its reported analysis for the primary result. Accordingly, the reported hazard ratio is the primary comparative estimate to interpret. The secondary recalculations are descriptive checks based on the posted summary information; they do not override or validate the sponsor’s primary analysis. The registry record does not give enough detail to reproduce the sponsor’s primary analysis independently.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or analyses are examined. Even if each analysis is conducted correctly, considering many results can increase the chance of finding an apparently notable result by chance. The registry lists a range of secondary outcomes, but a plan for controlling multiplicity, a testing hierarchy, and any division between confirmatory and exploratory analyses are not reported in the registry record. The recalculated secondary p-values are unadjusted, so they should not be read as multiplicity-controlled evidence.

The record identifies a full analysis set consisting of all participants randomized to study treatment and says participants were analyzed according to treatment and strata under the intention-to-treat principle. It also states that the full analysis set was the primary population for efficacy endpoint analysis at interim. This is useful information about the stated analysis population, but it does not give the complete analysis plan, clarify the analysis population for every posted endpoint, or describe how participants with incomplete outcome data were handled.

Missing-data methods are not reported in the registry record. For the primary time-to-event endpoint, details about censoring rules, loss to follow-up, and follow-up completeness are not reported. For the secondary binary endpoints, the record posts arm denominators and response counts, but does not explain how missing or unevaluable observations were treated or whether denominators varied by analysis rule. The registry does not report sensitivity analyses for missing data.

The primary endpoint timeframe refers to assessments every 8 weeks and to follow-up up to 10 months after futility was analyzed. The record also refers to an interim population. It does not report the timing, criteria, or statistical consequences of any interim or futility analyses. The original statistical analysis plan, including model details, covariate handling, and any interim error-control procedures, is not reported in the registry record. These gaps constrain assessment of the robustness of the efficacy findings.

16. 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: pyrexia (3.5%), pneumonitis (3.0%), cellulitis (2.5%), diarrhoea (2.5%), urinary tract infection (2.0%).

The safety listing reports serious adverse events affecting 61 of 202 participants in the BKM120 plus paclitaxel group and 42 of 201 participants in the placebo plus paclitaxel group. Other adverse events are listed for 196 of 202 and 188 of 201 participants, respectively. These are counts of affected participants as presented in the registry record; they are not measures of event duration or severity beyond the serious-event classification.

The listed serious adverse event terms include pyrexia (3.5%), pneumonitis (3.0%), cellulitis (2.5%), diarrhoea (2.5%), urinary tract infection (2.0%), and general physical health deterioration (1.5%). The record does not give further details about the definitions, attribution, timing, or exposure duration associated with these terms. Death counts are not reported in the registry record.

Safety denominators differ from the efficacy arm sizes described for progression-free survival. The registry does not explain the relationship between these analysis groups, so the safety and efficacy figures should not be compared as though they necessarily use the same population. These counts describe reported events; by themselves, they do not establish that treatment caused an event or quantify an individual’s risk.

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

The primary result describes progression-free survival in a randomized comparison of BKM120 plus paclitaxel with placebo plus paclitaxel among participants with HER2-negative, inoperable locally advanced or metastatic breast cancer. The posted medians and hazard ratio provide complementary summaries: the medians describe event timing within each group, while the hazard ratio is the comparative time-to-event estimate. The confidence interval around that comparative estimate is broad and spans values on either side of no difference.

These findings do not establish a precise direction or magnitude of a difference in progression-free survival. They also do not answer whether overall survival differed, since a numeric overall-survival result is not reported in the registry record. The listed secondary outcomes should not be treated as substitutes for the primary endpoint, especially where their analyses are unadjusted or results are not posted.

The findings apply to the trial population and the study comparison as described in the registry. They do not establish outcomes for people outside that population, for other treatment combinations, or under treatment schedules not described in the record. The record’s total enrollment and the primary efficacy population description do not fully align in a way that the registry explains, which further limits precise reconstruction of who contributed to each result.

Statistical uncertainty is not the same as proof of no effect, just as a point estimate on one side of no difference is not proof of an effect. The primary interval includes a range of plausible relative hazards, and the registry omits details that would help assess model assumptions, missing observations, and interim procedures. The appropriate reading is therefore bounded: the record reports an uncertain primary estimate and limited secondary results, without enough information to support a definitive claim about treatment effect.

Safety counts describe reported adverse events in the listed safety groups. They do not establish causation, and the registry does not report deaths or several details needed to interpret event exposure and attribution. These results should be read as the posted safety summaries rather than as a complete characterization of safety.

18. Why This Trial Matters Statistically

This trial is statistically informative because it reports a comparative time-to-event estimate alongside arm-specific medians. Those summaries illustrate why a median alone is not enough to characterize a randomized comparison: the median describes an event-time distribution within an arm, while the hazard ratio is the posted comparative measure. The confidence interval communicates that the comparative estimate is uncertain and allows readers to distinguish a point estimate from the range of values compatible with the analysis.

The record also demonstrates why endpoint families should remain distinct. Progression-free survival, response rate, clinical benefit rate, and overall survival address different outcomes. The two secondary outcomes with posted numeric results have unadjusted recalculations, while the other listed secondary outcomes have no numeric results reported in the registry record. This makes the distinction between primary and secondary evidence especially important.

Sample-size illustrations based on observed effects can help readers understand how targeted effect size affects planning, but they are not evidence that the completed trial had a particular probability of detecting an effect. Here, the original sample-size assumptions are not reported. That distinction prevents planning examples from being mistaken for a retrospective judgment about trial power.

Finally, the record exposes common interpretation limits in registry results: incomplete analysis-method detail, no reported multiplicity strategy, missing-data and censoring procedures not reported, and an unexplained relationship between overall enrollment and the primary efficacy population described. These gaps matter because the numerical estimate is only one component of statistical interpretation. Understanding the population, analysis process, and uncertainty is necessary to read the result responsibly.

19. 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 primary endpoint is described as local investigator-assessed progression-free survival, but central review procedures are not reported in the registry record. The analysis method field is not populated, and the record does not report whether the proportional-hazards assumption was assessed, how censoring was defined, or whether the primary model included covariates. The reported hazard ratio and confidence interval can be interpreted as posted, but the analysis cannot be fully reconstructed from the registry information.

The population description states that 338 participants were randomized for the primary efficacy analysis, while overall registry enrollment is 416. The registry does not explain the relationship between these figures. The safety groups have different denominators from the efficacy arms, and their relationship to the efficacy population is also not explained. These differences constrain direct comparisons across the reported outcomes.

The record lists multiple secondary outcomes but gives numeric results for only overall response rate and clinical benefit rate in the outcome data described. Numeric results for the remaining listed outcomes are not reported in the registry record. No multiplicity plan, missing-data strategy, or sensitivity analysis is reported. The unadjusted recalculated secondary comparisons therefore have limited inferential weight.

The outcome timeframe mentions assessments every 8 weeks and a period tied to futility analysis, while the primary population description refers to an interim analysis. Details of interim timing, decision rules, and the futility procedure are not reported. The original sample-size justification and design assumptions are also not reported, so the planning illustrations should not be mistaken for the trial’s own design calculations.

For safety, the registry supplies counts and selected serious adverse event terms, but not exposure-adjusted rates, event attribution details, or death counts. The available summaries are therefore incomplete for assessing the full safety profile. These limitations describe what is missing from the registry record; they do not establish that the information was absent from other trial materials.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation — NCT01572727.
• Registry record last updated 2017-03-09; status last verified 2017-01.
• Results first posted 2017-01-27.
• 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.

23. Record Summary

NCT01572727 is a completed randomized, quadruple-masked, parallel-group phase II/III study sponsored by Novartis Pharmaceuticals. It compared BKM120 plus paclitaxel with placebo plus paclitaxel in adult females with HER2-negative, inoperable locally advanced or metastatic breast cancer.

The primary outcome was local investigator-assessed progression-free survival. The registry reports medians of 8.0 months and 9.2 months, respectively, and a hazard ratio of 1.18 with a 95% confidence interval from 0.82 to 1.68. The interval indicates substantial uncertainty around the comparative estimate. Numeric secondary results are posted for overall response rate and clinical benefit rate; other listed secondary results are not reported in the registry record.

Important details, including the primary analysis method, multiplicity approach, missing-data procedures, interim-analysis plan, and original sample-size justification, are not reported in the registry record. The relationship between overall enrollment and the primary efficacy population description is also not explained.