Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC) (NCT02435680), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment).

2. Clinical Question

3. Trial Design

NCT02435680 is a randomized phase II study with a parallel-group design and no masking. Its official title describes MCS110 combined with carboplatin and gemcitabine in advanced triple negative breast cancer. The registry lists Novartis Pharmaceuticals as the sponsor and gives an enrollment of 50. The study status is completed; the recorded start date is 2015-08-10 and the primary completion date is 2020-01-04.

One arm received MCS110, carboplatin, and gemcitabine. The other received carboplatin and gemcitabine. The posted primary endpoint population is described as all MCS110-treated patients, with and without a day 8 dose, versus the comparator. This is important when reading the reported results: the MCS110 estimate is not presented as a separate result for only the day 8 dose subgroup.

The primary endpoint was progression-free survival per RECIST v1.1 by local investigator assessment, reported as a median in months and with a 90% confidence interval. The registry lists 34 participants for the MCS110 combination result and 16 for the carboplatin and gemcitabine result. The safety record uses different denominators: 34 for all MCS110-treated patients and 15 for the comparator group. Why the comparator denominators differ is not reported in the registry record.

The record lists 13 outcome measures and 12 posted secondary outcomes. These include pharmacokinetic measures, circulating CSF-1 levels, CTX-I, and tumor response and duration of response assessed by RECIST v1.1. The registry does not report the study’s sample-size justification, detailed treatment schedule, or a statistical analysis plan.

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: full analysis set: all MCS110 treated patients versus comparator

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 Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment), measured over 4 years.

Progression-free survival (PFS) is a time-to-event endpoint. In general, time-to-event measures describe how long it takes for a defined event to occur; the endpoint definition determines which events count and how follow-up is handled. Here, the registry identifies PFS assessed according to RECIST v1.1 by local investigator assessment, and states that results are presented as medians. Detailed rules for event handling and censoring are not reported in the registry record.

A median is the time by which half of the analyzed group has experienced the endpoint event, under the endpoint’s analysis rules. It describes the middle of the observed time-to-event distribution; it does not describe every participant’s experience or the shape of the full distribution. The reported unit is months. The MCS110 combination group had a median of 5.6 months, with a 90% confidence interval from 4.5 to 8.7. The carboplatin and gemcitabine group had a median of 5.5 months, with a 90% confidence interval from 3.5 to 7.5.

General statistical context: time-to-event endpoints can use information about when events occur and about participants whose event time is not observed during follow-up. A median provides an interpretable point on the distribution, while its confidence interval communicates uncertainty about that estimate. The registry does not give further details about censoring, follow-up completeness, or the method used to calculate the intervals.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the median describe?

The primary outcome is a time-to-event measure summarized by its median. In general, a median marks the point at which half of the analyzed observations lie on either side, according to the endpoint definition and analysis method. For PFS, the record specifies assessment per RECIST v1.1 by local investigator assessment, but it does not provide detailed rules for censoring or event determination. A median is a compact summary, not a complete account of the timing pattern across participants. Two groups can have similar medians while differing in other parts of their time-to-event distributions; the registry does not report enough detail to assess that possibility for this study.

What does a confidence interval communicate?

General statistical explanation: a confidence interval reflects the precision of an estimate under the assumptions and method used to calculate it. The reported 90% confidence interval for the MCS110 combination median extends from 4.5 to 8.7 months. For carboplatin and gemcitabine, it extends from 3.5 to 7.5 months. These intervals describe uncertainty about the estimated medians; they are not ranges of individual participant outcomes. The registry does not state the interval method or give details about assumptions used in its calculation.

Why is a direct comparison important?

Comparing two median estimates by inspection is not equivalent to estimating the treatment contrast with an inferential method. A direct comparison can use a relative measure such as a hazard ratio, accompanied by an uncertainty interval, if the study’s analysis supports that measure. The registry record reports no hazard ratio and no analysis for the two-arm comparison. It lists zero analyses. Accordingly, there is no posted inferential estimate to describe, and no basis in the registry record for interpreting the small difference between the reported medians as statistically established.

General statistical explanation: time-to-event analyses often use information from the timing of events and account for participants whose endpoint event is not observed by the end of their follow-up. Methods such as these rely on assumptions about follow-up and censoring. The registry record does not describe the censoring rules, follow-up distribution, or model used. The record’s endpoint description and summary statistics alone cannot establish which specific analytic approach was applied.

What do the sample-size illustrations represent?

Any sample-size figures associated with this analysis are planning illustrations based on fractions of the observed effect, not the trial’s original design calculations and not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the illustrations express the total number of events; for other outcomes, they express participants per arm. General statistical explanation: planning calculations describe the sample size or event count that a hypothetical design might require under its assumptions. They do not show the probability that a completed trial’s result is true, and they should not be described as observed power. The trial’s own sample-size justification is not reported in the registry record.

How should the reported groups be understood?

The primary endpoint description states that all MCS110-treated participants, including those with and without a day 8 dose, are included in the MCS110 result. The reported primary endpoint denominators are 34 and 16. The safety record lists 34 participants for all MCS110-treated patients and 15 for carboplatin and gemcitabine. The registry does not explain the difference between the comparator denominators or give additional details about analysis populations. The primary endpoint estimate should therefore be interpreted using the population description attached to that outcome, rather than assuming that every outcome used identical participants.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary PFS outcome and 12 posted secondary outcomes. Secondary outcomes include pharmacokinetic measures for free MCS110 and for carboplatin, gemcitabine, and dFdU; circulating CSF-1 levels; CTX-I; and tumor response and duration of response assessed by local investigator assessment per RECIST v1.1. The record does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment for evaluating multiple outcomes. It also does not give inferential analyses for the primary two-arm comparison.

Multiplicity matters because examining multiple outcomes or comparisons can increase the chance of at least one apparently notable result arising by chance. General statistical explanation: prespecified testing strategies can help control how results are interpreted across multiple analyses. Without a reported strategy, secondary findings should be considered descriptive unless their inferential context is available. The registry does not report a detailed statistical analysis plan, planned interim analyses, or a sample-size justification.

Missing-data handling is also not reported in the registry record. The posted primary endpoint denominators are 34 and 16, while the safety record lists 34 MCS110-treated participants and 15 comparator participants. The reason for the comparator denominator difference is not given. The registry does not explain whether participants were excluded from any outcome analysis, how incomplete follow-up was handled, or how missing measurements were addressed for secondary outcomes.

The primary endpoint population is described as all MCS110-treated patients, with and without a day 8 dose, versus the comparator. That description does not establish that all randomized participants were included in every analysis. Further details about allocation, exclusions, analysis populations, and missing observations are not reported in the registry record.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombocytopenia (20.0%), vomiting (13.3%), dyspnoea (13.3%), anaemia (6.7%), myocardial ischaemia (6.7%).

The safety record reports serious adverse events for 17 of 34 participants in the all-MCS110-treated group and 1 of 15 in the carboplatin and gemcitabine group. It reports other adverse events for 34 of 34 and 15 of 15, respectively. Deaths are listed for 2 of 34 all-MCS110-treated participants and 1 of 15 comparator participants. The overall safety entry lists 18 of 49 participants with a serious adverse event and 3 deaths among 49 participants. These are counts in the registry record, not estimates of comparative risk adjusted for differences between groups.

The listed serious adverse event terms include thrombocytopenia (20.0%), vomiting (13.3%), dyspnoea (13.3%), anaemia (6.7%), myocardial ischaemia (6.7%), and nausea (6.7%). The registry record does not provide the term-specific counts or explain the denominator used for each listed percentage. These terms should not be interpreted as a complete description of all adverse events or as evidence that a particular event was caused by a study treatment.

The safety groups include 19 participants in the MCS110 plus carboplatin and gemcitabine entry, 15 in the MCS110 with C1D8 dose entry, 34 in the combined MCS110 entry, and 15 in the carboplatin and gemcitabine entry. The record does not explain the relationship among all safety group entries in detail. The comparator safety denominator differs from the primary endpoint denominator, and the reason is not reported in the registry record.

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

The registry reports a median PFS of 5.6 months for all MCS110-treated participants and 5.5 months for participants receiving carboplatin and gemcitabine. Their 90% confidence intervals are 4.5 to 8.7 months and 3.5 to 7.5 months, respectively. These results describe the posted estimates and their uncertainty. They do not by themselves establish a comparative treatment effect.

The record does not report a hazard ratio, a p-value, or another inferential analysis of the two arms. Without such a result and its uncertainty, the difference between the medians cannot be interpreted as a statistically established contrast. The record also does not describe the statistical analysis plan, including prespecified decision criteria. A randomized design supports comparative evaluation, but the design label alone does not supply an estimate of effect or its precision.

The study’s primary endpoint population includes all MCS110-treated patients, with and without a day 8 dose. The results therefore do not provide a separate primary endpoint estimate for the day 8 dose subgroup. The primary outcome denominators are 34 and 16; the safety outcome uses 34 and 15. The reason for the different comparator denominators is not reported in the registry record.

The results also do not establish how PFS would compare in other populations or under other treatment schedules. The record identifies a population with advanced triple negative breast cancer and high TAMs, but does not give baseline characteristics or further eligibility details. The posted summary should therefore be read within the population and outcome definitions that the registry states.

General statistical explanation: an estimate is most informative when read alongside its uncertainty, the population analyzed, the outcome definition, and the method of comparison. In this case, the medians and intervals allow a descriptive account of PFS, while the absent direct comparison and unreported analysis details limit stronger statistical conclusions. No medical recommendation follows from these registry results alone.

13. Why This Trial Matters Statistically

This study is statistically notable as a randomized phase II comparison of a combination regimen with the same chemotherapy combination without MCS110. Random allocation is an important design feature for estimating comparative effects, while the parallel-group structure assigns participants to one of the two listed treatment approaches. The record also makes clear that the primary MCS110 result combines patients with and without a day 8 dose, a population detail that matters when interpreting the endpoint summary.

The record illustrates why a point estimate should not be read in isolation. Median PFS was 5.6 months in the MCS110-treated group and 5.5 months in the comparator group, but both estimates have 90% confidence intervals. Those intervals communicate uncertainty that a median alone would conceal. The registry does not post a hazard ratio or a statistical analysis for the direct comparison, so the primary results support description rather than a definitive comparative conclusion.

It also illustrates the importance of aligning populations and denominators across outcomes. The posted primary endpoint groups contain 34 and 16 participants, while the safety record lists 34 and 15. The reason for the comparator denominator difference is not reported. Readers should avoid assuming identical analysis populations across endpoint types when the record gives different counts.

Finally, the registry lists multiple secondary measures but does not report a multiplicity strategy or detailed statistical analysis plan. That makes it especially important to distinguish the stated primary endpoint from secondary measures and to avoid treating an isolated result as confirmatory without its analysis context. The record’s limits are part of the statistical interpretation: uncertainty, outcome definitions, analysis populations, and missing design details all shape what can reasonably be concluded.

14. 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 registry record leaves several trial-specific details unavailable. It does not report the sample-size justification, a detailed statistical analysis plan, interim analyses, or a prespecified decision criterion for the primary comparison. There is no posted hazard ratio or other inferential analysis for the two-arm PFS comparison. Consequently, the comparative precision and statistical evidence cannot be assessed from the reported medians alone.

The record reports PFS according to RECIST v1.1 by local investigator assessment, but does not describe the detailed event definition, censoring rules, or follow-up completeness. Masking is listed as none. The registry does not describe additional procedures intended to limit potential bias in local outcome assessment. These missing details constrain evaluation of how the endpoint was determined and analyzed.

The primary endpoint population is described as all MCS110-treated patients, with and without a day 8 dose, versus the comparator. The registry does not explain the comparator denominator difference between the primary endpoint results (16) and the safety record (15), nor does it provide a full account of analysis populations or exclusions. Enrollment was 50, while the overall safety entry lists 49 participants; the reason for that difference is not reported in the registry record.

The study lists 12 posted secondary outcomes in addition to the primary outcome, but no multiplicity approach is reported. Missing-data methods are also not reported. The record does not provide baseline characteristics or further eligibility information beyond the stated condition of advanced triple negative breast cancer with high TAMs. These limitations restrict assessment of comparability, generalizability, and the robustness of the posted findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC) — NCT02435680.
• Registry record last updated 2021-06-21; status last verified 2021-05.
• Results first posted 2021-06-21.
• 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.

18. Record Summary

NCT02435680 is a completed, randomized, unmasked, parallel-group phase II study sponsored by Novartis Pharmaceuticals. It enrolled 50 participants with advanced triple negative breast cancer and high TAMs. The study compared MCS110 plus carboplatin and gemcitabine with carboplatin and gemcitabine alone.

The primary endpoint was PFS per RECIST v1.1 by local investigator assessment, summarized as median time in months with 90% confidence intervals. The reported medians were 5.6 months for all MCS110-treated patients and 5.5 months for the comparator group. The registry lists 13 outcome measures and 12 posted secondary outcomes, but no analysis for the two-arm primary comparison. A hazard ratio, multiplicity strategy, missing-data methods, and detailed statistical analysis plan are not reported in the registry record.