Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer (NCT02785939), a non-randomized phase 2, phase 3 study. The primary outcome is Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial).

2. Clinical Question

The clinical question is about tumor response in a selected group with recurrent stage IV squamous cell lung cancer after previous treatment. The qualifying cell cycle gene alterations are part of the population definition, not an outcome. The registry describes the study as a phase II/III trial and lists palbociclib and docetaxel treatment arms, as well as re-registration to palbociclib for some participants who had received docetaxel.

The primary endpoint is an objective response rate rather than a time-to-event outcome. It asks whether participants experienced a complete or partial response, as defined by RECIST 1.1. The primary analysis was pre-specified for the palbociclib arm only, with the registry giving removal of docetaxel as standard of care treatment as the reason. The registry record does not report the response count, response percentage or confidence interval, so the size and precision of the observed response rate cannot be described from this record.

3. Trial Design

This Lung-MAP sub-study is listed as phase II/III, non-randomized, unmasked and parallel. Enrollment was 53. The sponsor was SWOG Cancer Research Network. The study began in 2014-09, had primary completion in 2017-06 and is marked completed. These registry entries describe the study framework; they do not provide the outcome estimate for the primary endpoint.

Three arms are described. In Arm I, participants received oral palbociclib on days 1–21, with courses repeating every 28 days unless progression or unacceptable toxicity occurred. This arm closed to accrual 09/01/2016. Arm II participants received intravenous docetaxel on day 1, with courses repeating every 21 days unless progression or unacceptable toxicity occurred. Participants with progression could be eligible to re-register to Arm III. Arm II closed to accrual 12/18/2015. Arm III was palbociclib re-registration for eligible participants from Arm II, using the palbociclib schedule; it closed to accrual 09/01/2016.

Non-randomized allocation means the record does not describe random assignment to palbociclib or docetaxel. The groups therefore should not be interpreted as randomized treatment groups with baseline comparability ensured by allocation. The registry specifically states that only the palbociclib arm would be analyzed for the primary endpoint because docetaxel was removed as standard of care treatment. It does not report a statistical analysis directly comparing the arms. The primary endpoint population is described as eligible and evaluable participants, but the record does not specify the number meeting that definition or the detailed evaluability rules.

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: 36 participants were initially enrolled to Palbociclib arm and 17 to Docetaxel. 5 participants on Palbociclib were ineligible. 5 participants on Docetaxel were ineligible, and 2 did not receive any protocol treatment. A participant on Docetaxel was re-registered to Palbociclib after progression on Docetaxel and is also included in Palbociclib arm analysis.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible and evaluable participants.

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: Eligible and evaluable participants

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial), measured over From date of registration to progression or treatment discontinuation, up to 2 years and 10 months..

The primary endpoint is objective response rate: the percentage of eligible and evaluable participants with a confirmed or unconfirmed complete or partial response to palbociclib. Responses were defined using RECIST 1.1. A complete response means disappearance of all target lesions; a partial response means at least a 30% decrease in the sum of the longest diameters of target lesions. Overall response combines complete and partial responses.

A response endpoint reduces each participant’s assessment to a category: response or no response under the endpoint definition. The resulting percentage is a direct description of how often response was recorded in the analyzed population. It does not, on its own, describe how long a response lasted, whether disease remained controlled, or how long participants lived. The registry lists duration of response, overall survival and progression-free survival among secondary outcomes, which address different aspects of outcomes.

The endpoint timeframe is from registration to progression or treatment discontinuation, up to 2 years and 10 months. The registry states that only the palbociclib arm was to be analyzed for this endpoint. It specifies a 95% confidence interval as the measure of uncertainty, but does not report an observed response percentage, response count or confidence interval in the record. Consequently, the endpoint definition is available, while the primary result and its precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is binary at the participant level: each eligible and evaluable participant is classified according to whether a complete or partial response was recorded under RECIST 1.1. The response rate is the percentage of participants in the analysis population who meet that definition. This kind of endpoint is useful when the research question concerns the frequency of a defined event, rather than the time until an event. The registry gives the endpoint unit as percentage of participants and specifies a 95% confidence interval.

What does a confidence interval add?

A point estimate alone does not show how much uncertainty is associated with it. A confidence interval uses the observed data and a statistical procedure to describe uncertainty around an estimate. In repeated use of a method under its assumptions, intervals constructed in this way have a stated coverage property. The interval is not a guarantee that a particular range contains the true value, nor does it account automatically for every possible source of bias. The registry record gives the intended interval level but does not report the interval or the observed response estimate.

For a percentage, the width of an interval depends in part on how many participants contribute data and how responses are distributed. A small analysis population can leave substantial uncertainty even when the point estimate appears clear. In this study, the registry reports enrollment of 53 but defines the primary endpoint population as eligible and evaluable participants. It does not report that population’s size, so the precision cannot be reconstructed from the enrollment figure.

Why does the analysis population matter?

The denominator determines what population the response percentage describes. An eligible-and-evaluable population is not necessarily identical to everyone enrolled. The registry names the intended population but does not report its count or provide detailed rules for eligibility, evaluability, missing assessments or exclusions from analysis. Without those details and the outcome counts, neither the analysis population nor its response rate can be independently checked.

RECIST 1.1 supplies operational definitions for response. The record describes complete response as disappearance of all target lesions and partial response as at least a 30% decrease in the sum of the longest diameters of target lesions. Combining these categories into overall response makes the primary endpoint a single proportion. Including confirmed and unconfirmed responses is part of the endpoint wording; the record does not provide separate counts for those categories. The timeframe runs from registration to progression or treatment discontinuation, up to 2 years and 10 months.

What can non-randomized allocation support?

Random allocation is one way to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. This study is listed as non-randomized, and the registry says the primary analysis was planned for the palbociclib arm only. The docetaxel arm is therefore not a randomized comparator for that primary endpoint. Descriptive outcomes in the two arms would not alone establish that treatment caused any difference. The record does not report covariate-adjusted analyses, a comparative statistical model or other methods intended to address differences between groups.

The parallel model indicates that the trial includes distinct treatment arms, while the arm descriptions also include a route from docetaxel to possible palbociclib re-registration after progression. The record lists the schedules and accrual closures but does not report a statistical method for handling re-registration in an analysis. The primary endpoint’s stated focus on the palbociclib arm should be kept separate from the presence of other arms in the study.

How should planning illustrations be read?

The planning assumptions describe illustrations based on the observed effect. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and an effect expressed as a stated fraction of the observed effect. Such calculations illustrate how a hypothetical design might perform under specified assumptions; they do not report what happened in the trial. The stated equal allocation is an assumption for the illustration, not evidence that the non-randomized study assigned equal numbers to its arms. The numerical effect and planning outputs are not reported in the registry record details for this account.

Power calculations made using an observed effect are especially dependent on that effect estimate and its uncertainty. They should be read as planning illustrations, not observed power and not proof that a study was adequately or inadequately designed. The record does not report a sample-size justification for the original trial, so the illustration should not be mistaken for the original protocol’s rationale.

What information is missing for statistical assessment?

The registry record does not report a primary response count, response rate, confidence interval, detailed missing-data approach, or a full statistical analysis plan. It also does not report whether the primary endpoint analysis used an intention-to-treat approach or another analysis population beyond the eligible-and-evaluable description. These omissions prevent a detailed assessment of endpoint precision, analysis choices and robustness. They do not change the endpoint definition, but they limit what can be concluded about the results from the record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Palbociclib")
n      <- c(32)
events <- c(2)
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  Palbociclib  32  2  6.2  0.8  20.8  1.7  20.1  1.9  20.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists an objective response rate as the primary endpoint and lists several secondary outcomes: duration of response among participants with complete or partial response, overall survival with investigational therapy, progression-free survival with palbociclib, and participants with Grade 3 through 5 adverse events related to study drugs. It reports seven outcome measures in total. Considering multiple outcomes can raise the chance of at least one apparently notable result when many statistical tests are conducted. Whether and how that concern was addressed depends on the analysis plan.

Multiplicity procedures, any hierarchy of hypotheses, and any adjustment to significance levels are not reported in the registry record. The record also does not report a complete set of outcome analyses; its analysis count is 0. The absence of a reported adjustment does not establish that none was planned outside the registry record, but no such method can be described from this record.

Missing-data methods are also not reported. The endpoint is defined for eligible and evaluable participants, but the record does not give the number in that population or explain how missing, incomplete or unevaluable response assessments were treated. It does not report whether participants who stopped treatment or lacked an assessment were counted as non-responders, excluded, or handled in another way. These choices can affect the denominator and the resulting percentage.

For these reasons, the endpoint definition is clearer than the analysis details. The registry record does not report a detailed statistical plan, missing-data handling, or the primary result needed to assess the consequences of those choices.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (9.4%), lung infection (9.4%), lymphocyte count decreased (9.4%), neoplasms benign, malignant and unspecified - other (9.4%), dyspnea (9.4%).

The registry’s serious-event summary lists 32 participants at risk in the palbociclib group, with 14 affected, and 10 participants at risk in the docetaxel group, with 0 affected. The summary also lists other adverse events affecting 31 of 32 participants in the palbociclib group and 10 of 10 in the docetaxel group. These are descriptive counts for the groups recorded; the non-randomized design means they should not be treated as a controlled comparison of safety.

The listed deaths are 28 in the palbociclib group and 10 in the docetaxel group. A death count does not, by itself, establish that a study drug caused the death. The record’s secondary outcome description separately refers to Grade 3 through 5 adverse events related to study drugs, but the serious-event summary should not be assumed to represent that specific outcome definition.

The most frequent listed serious-event terms include Anemia, Lung infection, Lymphocyte count decreased, Neoplasms benign, malignant and unspecified - Other, and Dyspnea, each recorded as 9.4%; White blood cell decreased is listed as 6.2%. These terms and percentages describe the registry’s listed events. The record does not provide further detail about event timing, participant overlap across terms, attribution or a comparative statistical analysis. They should be read as descriptive safety information, not as proof of a treatment effect or a treatment-related cause.

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

The registry record establishes the intended question and the way the primary outcome was defined. It describes a study of palbociclib in previously treated, cell cycle gene alteration-positive participants with stage IV squamous cell lung cancer, and identifies the percentage with complete or partial response under RECIST 1.1 as the primary endpoint. The record also states that only the palbociclib arm was to be analyzed for this outcome.

What the record does not establish is the observed response rate. No primary response count, percentage or confidence interval is reported. Without those quantities, the frequency of response and its precision cannot be assessed. A study’s endpoint definition is not itself evidence about the size of the result; interpretation requires the observed data and enough analysis detail to understand the population and methods.

The trial’s non-randomized allocation also limits what can be inferred from comparisons between arms. The docetaxel group should not be read as a randomized control group, and the registry does not report a comparative analysis for the primary endpoint. Differences between arm summaries could reflect differences in the participants or other factors as well as treatment, and the record does not describe an adjustment strategy.

The listed adverse-event information is descriptive. The serious-event counts, other adverse-event counts and deaths do not establish causation, and they do not replace the separately listed outcome concerning Grade 3 through 5 adverse events related to study drugs. The record does not report enough detail to assess event timing or attribution beyond the listed summaries.

Thus, the registry supports a description of the study’s population, treatment structure, endpoint and listed safety counts. It does not support a numerical conclusion about the primary response result, its precision, or a causal comparison between palbociclib and docetaxel. The record’s limitations should be kept distinct from claims about results that it does not report.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry clearly specifies an objective response rate based on RECIST 1.1 and identifies the intended population as eligible and evaluable participants. Yet the record does not give the response count, percentage or confidence interval. Without those results, the statistical question of how frequently response occurred and how precisely it was estimated remains unanswered by the record.

It also highlights the importance of design when interpreting treatment groups. The study is non-randomized, and the registry says the primary analysis was planned for the palbociclib arm only. The presence of a docetaxel arm does not make it a randomized control for the palbociclib analysis. Keeping descriptive arm information separate from a causal comparison is essential for sound interpretation.

The distinction between enrolled participants and an analysis population matters as well. Although enrollment was 53, the primary population is defined as eligible and evaluable participants, and its size is not reported. A percentage without a clear denominator cannot be independently interpreted or checked. Reporting analysis populations, endpoint counts and uncertainty measures is therefore central to statistical transparency.

Finally, the study record lists multiple secondary outcomes and safety summaries, but does not report multiplicity methods, missing-data handling or a detailed statistical analysis plan. These are not merely technical details: they help readers understand how results were selected, how incomplete observations were treated and what comparisons were intended. The record’s gaps make it important to distinguish what was specified from what was actually reported.

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 most important limitation for interpreting the primary endpoint is that the registry record does not report its result. There is no response count, response percentage or 95% confidence interval. The number of eligible and evaluable participants is also not reported, so enrollment of 53 cannot be used as the primary analysis denominator.

The record does not report detailed rules for determining evaluability, treatment of missing or incomplete response assessments, or the analysis population beyond the eligible-and-evaluable description. It also does not report a full statistical analysis plan, multiplicity procedures, or methods for any adjusted or comparative analysis. The absence of those details limits assessment of how analyses were conducted; it does not establish what may or may not have been specified elsewhere.

Because allocation was non-randomized, the arm descriptions do not support a like-for-like randomized comparison. The registry explicitly states that the primary endpoint would be analyzed only in the palbociclib arm. It does not report a primary between-arm analysis or methods addressing possible group differences. The docetaxel and palbociclib summaries should therefore be interpreted descriptively rather than as a causal contrast.

The safety information is also limited in what it can establish. The record lists affected participants, deaths and selected serious-event terms, but does not provide detailed timing, overlap between event categories or enough information to attribute deaths to study treatment. The listed Grade 3 through 5 adverse-event outcome is not accompanied by a result in the record details for this account.

Finally, the planning assumptions are described as illustrations based on the observed effect, rather than as the trial’s own design justification. The original sample-size justification is not reported in the registry record. These constraints mean the record offers useful design and endpoint definitions but a limited basis for evaluating efficacy results, precision, comparative effects or the full safety profile.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer — NCT02785939.
• Registry record last updated 2021-05-27; status last verified 2021-05.
• Results first posted 2021-05-27.
• 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.

19. Record Summary

The registry record describes a completed, non-randomized Lung-MAP sub-study, listed as phase II/III, of palbociclib in previously treated participants with cell cycle gene alteration-positive stage IV squamous cell lung cancer. Enrollment was 53. The record lists palbociclib, docetaxel and palbociclib re-registration arms, with accrual closures specified for each.

The primary endpoint was objective response rate, including confirmed and unconfirmed complete or partial responses under RECIST 1.1, among eligible and evaluable participants. The registry states that only the palbociclib arm would be analyzed for this endpoint. Although the endpoint definition and a 95% confidence interval are specified, the primary response count, percentage and interval are not reported in the registry record.

Secondary outcomes include duration of response, overall survival, progression-free survival and Grade 3 through 5 adverse events related to study drugs. The record also lists serious and other adverse-event summaries. Non-randomized allocation, missing analysis details and the absence of primary outcome results limit interpretation of treatment effects and precision.