A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor (HER)2 Immunohistochemistry (IHC)-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor (HER)2 Immunohistochemistry (IHC)-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (NCT02289833), a na phase 2 study. The primary outcome is Percentage of Participants With Objective Response as Per Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1).

2. Clinical Question

3. Trial Design

This was a Phase 2, multicenter, single-arm study of trastuzumab emtansine in HER2 IHC-positive participants with locally advanced or metastatic NSCLC. The record lists an enrollment of 49 and a completed status. The study started on 2014-12-15, and primary completion was recorded as 2016-10-25. These dates describe the registry record; they do not establish the follow-up time for every participant.

The two cohorts were defined by HER2 IHC status: IHC 2+ and IHC 3+. The cohort descriptions state that participants had received at least one prior platinum-based chemotherapy regimen. Both cohorts received the same study drug, so the cohort distinction is not a randomized comparison of treatments. Differences between cohort outcomes, if available, would not by themselves establish that IHC status caused a difference in response.

Trastuzumab emtansine was administered intravenously at 3.6 milligrams per kilogram on Day 1 of 21-day cycles. Treatment was planned to continue until disease progression assessed by the investigator, unmanageable toxicity, or study termination by the sponsor, whichever occurred first. The study was unmasked, with no masking listed.

The registry describes objective response as the primary endpoint and lists several secondary outcomes, including overall survival, progression-free survival, duration of response, clinical benefit, and adverse events. However, it reports no analysis results for the primary endpoint and lists zero analyses. The registry record does not report the allocation of participants between cohorts beyond the adverse-event risk counts, or give a statistical analysis plan, sample-size justification, or interim-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: The efficacy-evaluable population included participants who received at least one dose of study drug.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Objective Response as Per Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1), measured over From Day 1 to disease progression (PD) or death from any cause, up to the clinical cutoff date (approximately 22 months).

The primary endpoint is the percentage of participants with an objective response according to investigator assessment using RECIST version 1.1. Objective response requires a complete response or partial response confirmed on two consecutive assessments at least 4 weeks apart. A complete response requires disappearance of target lesions, with pathological lymph nodes reduced to less than 10 millimeters in short axis. A partial response requires at least a 30% decrease in the sum of target-lesion diameters relative to baseline.

A response percentage expresses how often the defined outcome occurred in the assessed population. It provides a compact measure of tumor response under the study’s assessment rules, while the confidence interval conveys uncertainty around that estimate. Confirmation across consecutive assessments is part of the stated endpoint definition, not an additional analysis result.

The endpoint timeframe runs from Day 1 to disease progression or death from any cause, up to the clinical cutoff date, described as approximately 22 months. The efficacy-evaluable population included participants who received at least one dose of study drug. The registry record reports the endpoint definition and a 95% confidence interval as the dispersion measure, but does not report the response estimate or its interval. The observed endpoint therefore cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-arm design estimate?

In a single-arm study, participants receive the study intervention without a concurrent control group. The primary response percentage is therefore an estimate of the proportion meeting the response definition among the assessed participants. It is not a direct estimate of the difference between treatments. Comparisons with results from other studies can be difficult because populations, eligibility rules, assessment practices, and follow-up may differ. The registry identifies no randomized comparison, and the IHC cohorts are not control groups because both received trastuzumab emtansine.

How should a response percentage be read?

A percentage is a summary of how frequently an outcome occurred in a defined population. Its meaning depends on the endpoint definition and who was included in the denominator. Here, the registry defines the efficacy-evaluable population as participants who received at least one dose. The primary endpoint is objective response assessed by the investigator according to RECIST version 1.1, with a response requiring confirmation on two consecutive assessments at least 4 weeks apart. The registry record does not report the numerator or the response percentage, so no observed estimate can be interpreted.

What does the confidence interval add?

A confidence interval describes the statistical uncertainty around an estimate under the method used to calculate it. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not show the range of outcomes for individual participants, and it does not correct for limitations such as lack of a control arm or potential selection and assessment biases. The registry lists a 95% confidence interval as the primary endpoint’s dispersion measure, but the interval itself is not reported in the registry record. Its width and compatibility with different response rates therefore cannot be assessed.

Why does the endpoint definition matter?

RECIST version 1.1 provides rules for classifying tumor response based on lesion measurements. Under this record’s definition, complete response and partial response have distinct criteria, and objective response requires one of those categories to be confirmed on consecutive assessments. These rules determine which participants count as responders. Investigator assessment identifies who performed the assessment; the registry record does not report an independent review process. The endpoint’s specified timeframe is from Day 1 to progression or death, up to a clinical cutoff described as approximately 22 months.

How do the secondary outcomes differ?

The listed secondary outcomes include binary outcomes, such as whether a participant had a progression-free survival event, and time-to-event outcomes, such as overall survival and progression-free survival. A binary outcome classifies participants according to whether an event occurred within a defined assessment framework. A time-to-event outcome uses the time until an event and may also involve censoring when the event is not observed during follow-up. General statistical practice treats these outcome types differently because they answer different questions. The registry record does not report the estimates, event times, censoring rules, or analysis methods for these secondary outcomes.

What can the sample-size assumptions establish?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns the total number of events; for other outcomes, it concerns participants per arm. These are planning assumptions, not observed trial results and not observed power. They also do not establish the trial’s original design rationale. A sponsor’s sample-size justification is not reported in the registry record, and no planning illustration can replace the missing endpoint estimate.

What does the absence of analysis results mean?

The registry lists zero analyses. Consequently, it does not provide an estimate for the primary endpoint or the listed secondary outcomes. The presence of an endpoint definition is not evidence that its result was posted, and a completed study status is not itself an outcome. Without estimates and uncertainty measures, readers cannot judge the size or precision of the response result from this record. The registry record does not report the statistical model, any covariate adjustment, handling of missing assessments, multiplicity procedures, or interim analyses. Those methods should not be inferred from the study phase, endpoint type, or sample-size assumptions.

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("Cohort IHC2+", "Cohort IHC3+")
n      <- c(29, 20)
events <- c(0, 4)
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  Cohort IHC2+  29  0  0.0  0.0  11.9  0.0  11.7  0.1  11.6
ARM  Cohort IHC3+  20  4  20.0  5.7  43.7  8.1  41.6  8.2  41.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and multiple secondary outcomes, including mortality, overall survival, progression-free survival, duration of response, clinical benefit, and adverse events. When several outcomes are examined, multiplicity can arise because repeated statistical testing increases the chance of at least one apparently notable result under general statistical principles. Whether adjustment is appropriate depends on the study’s objectives and prespecified analysis plan. The registry record does not report a multiplicity strategy, a testing hierarchy, or adjusted analyses, so it is not possible to determine how multiple outcomes were handled.

Missing outcome data can affect both the denominator and interpretation of a response percentage. For example, participants without adequate assessments may not be classifiable under the response definition. The efficacy-evaluable population is described as participants who received at least one dose, but rules for missing or unevaluable assessments are not reported in the registry record. The record also does not report whether all enrolled participants received a dose or how participants who discontinued treatment were handled in each analysis.

For time-to-event outcomes, incomplete follow-up may require censoring, but censoring rules and follow-up summaries are not reported in the registry record. The planned timeframe for the primary endpoint is described, but that does not establish individual follow-up completeness. Analysis populations for secondary endpoints, the handling of protocol deviations, and any sensitivity analyses are also not reported. The registry therefore does not allow an assessment of whether missingness or analysis choices could have affected the posted estimates; the estimates themselves are not reported.

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: abdominal pain (5.0%), pneumonia (5.0%), craniocerebral injury (5.0%), subdural haematoma (5.0%), tumour pain (5.0%).

The serious-adverse-event record lists 5 affected participants among 29 at risk in Cohort IHC2+ and 5 among 20 at risk in Cohort IHC3+. The listed deaths are 23 in Cohort IHC2+ and 16 in Cohort IHC3+. These are cohort-level counts, not evidence that an adverse event or death was caused by trastuzumab emtansine. The record does not provide enough detail to establish event timing, duration of exposure, or causal attribution.

The listed serious-event terms—abdominal pain, pneumonia, craniocerebral injury, subdural haematoma, tumour pain, and pulmonary embolism—are each reported with a value of 5.0%. The term-specific denominators and whether the listed terms overlap within participants are not reported in the registry record. The percentages should therefore be read as registry-reported figures, not converted into participant counts or added together. Counts and percentages also do not indicate comparative risk because the study has no control arm. A complete interpretation would require the event definitions, exposure and follow-up context, and attribution details, which are not reported in the registry record.

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

The study addresses the frequency of investigator-assessed objective response in participants with HER2 IHC-positive, locally advanced or metastatic NSCLC treated with trastuzumab emtansine after prior chemotherapy. Its primary endpoint has a defined response framework based on RECIST version 1.1, including confirmation on consecutive assessments. The study also lists survival, progression, response-duration, clinical-benefit, and safety outcomes.

However, the registry record does not report the primary response estimate or its confidence interval, and it lists zero analyses. It therefore does not show how many participants met the response definition or how precisely any response percentage was estimated. The listed secondary outcomes also have no reported analysis results in the registry record. A completed status and a defined endpoint cannot substitute for outcome estimates.

The single-arm design permits descriptive assessment of outcomes among participants who received the study drug, but it does not provide a randomized comparison. The two HER2 IHC cohorts both received trastuzumab emtansine, so they cannot serve as treatment and control groups. Any difference between cohorts would need cautious interpretation and would not establish a causal treatment effect.

The record’s safety counts and listed serious-event terms describe reported events, but they do not establish treatment causation or comparative safety. Missing information about event attribution, follow-up, and exposure limits interpretation. In general, an outcome estimate describes the observed data, while causal conclusions require an appropriate comparison and careful attention to design and analysis. The registry record supports understanding what the study set out to evaluate, but the absent efficacy analyses prevent an assessment of the observed primary result.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between a clearly defined endpoint and a reported endpoint result. The registry specifies an investigator-assessed objective-response measure, its RECIST version 1.1 criteria, the confirmation rule, and a confidence-interval measure. Yet it does not report the response estimate or interval. Statistical interpretation depends on both the endpoint’s definition and the numerical result; one cannot infer the latter from the former.

The single-arm structure also makes the estimand important. A response percentage in participants receiving one intervention is descriptive of that study group. Without a concurrent control arm, it does not estimate a randomized contrast. The separate IHC 2+ and IHC 3+ cohorts may be clinically and biologically distinct groups, but both received the same intervention, so their existence does not create a control comparison.

The study further highlights why statistical precision and design strength are different considerations. A confidence interval, if reported, would describe uncertainty around the response estimate; it would not remove the limitations of a nonrandomized, single-arm design. Similarly, planning illustrations based on an observed effect are not trial results or observed power. They cannot supply information that is absent from the analysis record.

Finally, the registry lists several secondary efficacy and safety outcomes but no analysis results. This makes the distinction between registered outcomes and available evidence especially important. Readers can identify the intended questions and the recorded safety counts, while recognizing that the registry record does not provide the analyses needed to assess the primary result or compare outcomes across treatments.

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 central limitation for statistical interpretation is that the registry record does not report results for the primary endpoint or the listed secondary outcomes. The response count, response percentage, and confidence interval are not reported. The record lists zero analyses, so the observed efficacy result cannot be evaluated from the registry entry.

The study is single-arm and has no randomized comparator. Its design can describe outcomes among treated participants but cannot estimate a treatment effect relative to a control group. The IHC 2+ and IHC 3+ cohorts both received trastuzumab emtansine and are not like-for-like control groups. The record does not report a statistical plan for comparing those cohorts, and any comparison between them would need to account for their nonrandomized grouping.

The primary outcome is based on investigator assessment. The registry record does not report whether an independent review was conducted, how missing or unevaluable assessments were handled, or whether sensitivity analyses were performed. Although it defines the efficacy-evaluable population as participants who received at least one dose, it does not provide full analysis-population details or clarify how participants without adequate response assessments were treated.

For safety, the record includes cohort counts and selected serious-event terms, but detailed event timing, attribution, exposure context, and term-specific denominators are not reported. It also does not report the statistical methods for secondary time-to-event outcomes, including handling of censoring. These omissions limit interpretation of both efficacy and safety beyond the design and counts explicitly recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor (HER)2 Immunohistochemistry (IHC)-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) — NCT02289833.
• Registry record last updated 2019-08-07; status last verified 2019-07.
• Results first posted 2017-11-22.
• 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

NCT02289833 is a completed Phase 2, multicenter, single-arm study of trastuzumab emtansine in HER2 IHC-positive, locally advanced or metastatic NSCLC. The registry records an enrollment of 49, with IHC 2+ and IHC 3+ cohorts. Participants received intravenous trastuzumab emtansine at 3.6 milligrams per kilogram on Day 1 of 21-day cycles, with treatment planned until progression, unmanageable toxicity, or sponsor termination.

The primary endpoint was investigator-assessed objective response according to RECIST version 1.1. The registry record defines the endpoint but does not report its estimate or confidence interval; it lists zero analyses. Secondary outcomes are also listed without analysis results. Safety entries include serious-event and death counts by cohort, but detailed attribution and event context are not reported in the registry record.