Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer (NCT01037790), a non-randomized phase 2 study. The primary outcome is Response Rates.

2. Clinical Question

The study rationale describes PD-0332991 as a drug intended to block enzymes needed for tumor-cell growth. Its stated purpose was to study side effects and how well the drug works in patients with refractory solid tumors. The design can describe outcomes among people treated in each group, but without a concurrent control it cannot establish how those outcomes compare with another treatment or with no study treatment.

3. Trial Design

This is a completed Phase II study with a reported enrollment of 304. It began in 2009-10, and its primary completion was recorded as 2019-10. The registry classifies the allocation as nonrandomized, masking as none, and the model as single group. These labels indicate that the record does not describe randomized assignment to treatment alternatives or masking of treatment allocation.

The intervention was PD-0332991. Five arm descriptions define populations by cancer type or tumor characteristic: metastatic breast cancer; metastatic colorectal cancer harboring a Kras or BRAF mutation; advanced or metastatic esophageal and/or gastric cancer; cisplatin-refractory, unresectable germ cell tumors; and tumors with specified CCND1, CDK4/6, or CCND2 alterations, or another functional alteration at the G1/S checkpoint. The registry describes oral administration at 125 mg QD on a 21-day schedule. Further detail about the schedule is not reported in the registry record.

Although the record uses a single-group model classification, it separately describes these five tumor-defined groups. They should not be read as treatment arms in a comparative trial: the groups differ by eligibility-defining cancer types and molecular features, and treatment allocation was not randomized. The number enrolled in each group is not reported in the registry record.

The registry lists one primary outcome measure, response rates, assessed using RECIST over a timeframe of 10 years. The record does not give a more specific schedule for when individual response assessments were made. It also describes adverse-event summaries by group. The registry status is completed, but completion status does not by itself mean that outcome estimates or a statistical analysis are posted.

The sponsor is Abramson Cancer Center at Penn Medicine. The registry record does not report the protocol-level rationale for the enrollment target, detailed eligibility criteria for each group, or a full treatment schedule. Those omissions limit how precisely the trial's planned procedures can be reconstructed from the 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.

Overall Study

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 Response Rates, measured over 10 years.

The primary endpoint is response rate, reported as a count of participants and assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). The registry describes complete response as disappearance of all target lesions. Partial response is defined as an ≥30% decrease in the sum of the longest diameters of target lesions compared with baseline. Progressive disease is defined as an ≥20% increase in that sum compared with the smallest sum recorded since treatment started, or the appearance of one or more new lesions. Stable disease is neither partial response nor progressive disease; the record also includes a not-evaluable category.

In general, a categorical response endpoint turns measurements of tumor lesions into clinically interpretable categories. It can summarize how many participants met each response category under the trial's assessment criteria. The criteria also specify how to distinguish changes in measured lesions from the appearance of new lesions, which may classify disease as progressive even without a qualifying increase in the measured sum.

The registry lists the response outcome timeframe as 10 years, but it does not provide participant-level assessment dates, category counts, response rates, or uncertainty intervals. Therefore, the endpoint definition is available, while the observed response result is not reported in the registry record. The record also does not describe how not-evaluable participants were handled in a response-rate denominator.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies response as a binary or categorical outcome measured by participant counts. For this type of endpoint, an analysis would ordinarily classify each participant according to the response criteria and then summarize the number meeting the outcome definition. The registry record provides the categories and lesion-change rules, but it does not report the response counts, the denominator used for a response-rate estimate, or a statistical analysis of the endpoint.

What does a response rate describe?

In general, a response rate is the proportion of an analysis population that meets a defined response criterion. The numerator depends on which response categories count as a response, and the denominator depends on which participants are included. Those choices should be stated because excluding people without an evaluable assessment can produce a different estimate from counting them as nonresponders. The registry includes complete response, partial response, progressive disease, stable disease, and not evaluable in its endpoint description. How the not-evaluable category was incorporated into an analysis is not reported in the registry record.

Why does the study design matter?

Randomization is a general method for making treatment groups comparable, on average, with respect to both measured and unmeasured baseline characteristics. This study is recorded as nonrandomized and single group, with no masking. Its five described groups have different tumor-based eligibility characteristics. Accordingly, the record does not support a randomized between-treatment effect estimate. A descriptive response estimate within a group, if available, would characterize that treated group, while a comparison across groups would be confounded by their different cancer populations and would not represent a controlled treatment contrast.

What does an uncertainty interval add?

In general, a confidence interval gives a range of values compatible with the data under the statistical method used. It helps readers distinguish a relatively precise estimate from one with substantial uncertainty. An interval does not remove design limitations or establish causation. No response estimate or confidence interval is reported in the registry record, so neither the size nor precision of a response result can be assessed from this record.

How should planning calculations be read?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also specifies that the effect to detect is a stated fraction of the observed effect. In general, sample-size calculations estimate the number of participants needed under selected assumptions to detect a specified effect with a chosen probability and significance threshold. They are conditional on those assumptions and do not describe what the study actually observed. The record does not state a protocol sample-size justification or report an observed response effect to use in evaluating a calculation. Any sample sizes from such an illustration should therefore be understood as planning illustrations, never as observed power.

Why can event counts need more context?

Adverse-event counts summarize participants with reported events, but interpretation depends on definitions, follow-up, exposure, event severity, and whether events were assessed consistently. In general, an event occurring during a trial is not automatically an event caused by the intervention. A controlled comparison can help quantify differences in event frequency, but this study has no randomized control group. The registry posts group-level counts and selected serious-event terms; detailed event-level timing, duration, recurrence, attribution, and complete analysis methods are not reported in the registry record.

The statistical analysis plan, including any prespecified models, confidence-interval methods, handling of missing assessments, and analysis populations, is not reported in the registry record. The record lists no outcome analysis entries. Therefore, the methods that generated efficacy estimates cannot be assessed, because efficacy estimates are not posted. General statistical principles can explain what such analyses would mean, but they cannot replace the missing study-specific methods and results.

10. Multiplicity, Missing Data and Analysis Populations

The trial describes five tumor-defined groups and a primary response-rate outcome. When multiple groups or outcomes are assessed, general statistical practice considers whether multiplicity adjustments or a hierarchy of hypotheses are needed to control the chance of false-positive findings. The registry record does not report a multiplicity strategy, a hierarchy of tests, or whether any such procedure was planned. It also does not post response analyses, so there are no reported efficacy tests to interpret in light of multiplicity.

The record lists one primary outcome measure and gives RECIST response categories, but does not describe an analysis population for that endpoint. It does not specify whether all enrolled participants, treated participants, or only those with evaluable assessments were included in a response denominator. The handling of participants without a post-baseline assessment and the treatment of the not-evaluable category are not reported in the registry record.

In general, missing outcome data can affect an estimate when the chance that an outcome is missing is related to the participant's underlying response or clinical status. Statistical handling may include explicit missing-data assumptions or sensitivity analyses, but the appropriate approach depends on the study design and data. Missing-data methods, reasons for missing assessments, and sensitivity analyses are not reported in the registry record.

The record also does not report whether any interim analyses were planned or conducted. Because no outcome analysis entries are posted, the analysis populations, analysis timing, and methods for handling multiple comparisons or missing response assessments cannot be evaluated.

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: leukopenia (33.3%), neutropenia (33.3%), lymphopenia (31.6%), anemia (26.3%), thrombocytopenia (18.2%).

The registry reports adverse-event summaries separately for Arm 1 through Arm 5. For each group, it gives the number at risk and the number affected by serious adverse events, the number at risk and the number affected by other adverse events, and deaths. For example, the serious-event figures are 1 of 63 in Arm 1, 10 of 18 in Arm 2, 11 of 19 in Arm 3, 10 of 30 in Arm 4, and 4 of 11 in Arm 5. The reported deaths are 0, 0, 1, 0, and 1, respectively. These are descriptive counts in groups with different tumor characteristics, not randomized safety comparisons.

The record lists leukopenia and neutropenia at 33.3% each, lymphopenia at 31.6%, anemia at 26.3%, thrombocytopenia at 18.2%, and elevated alk phos at 15.8% among the top serious terms. These percentages should be read as the registry's reported summaries; the record does not provide full event-level details alongside them. In general, a serious adverse-event count describes participants meeting the serious-event definition, whereas a term-specific summary describes particular reported event types. A participant may have more than one event, so event terms should not automatically be treated as mutually exclusive.

The registry's counts do not establish that an event was caused by the drug. Event attribution, timing, duration, and detailed severity information are not reported in the registry record. Because there is no randomized control group, the figures do not provide a controlled estimate of excess risk relative to another treatment.

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

The registry record establishes that this was a completed Phase II study of PD-0332991 in several tumor-defined populations and that response rate assessed by RECIST was the primary outcome. It also records group-level adverse-event counts and a list of selected serious adverse-event terms. These registry entries describe the study's scope and the kind of outcome it intended to measure.

The record does not report response counts, response rates, uncertainty intervals, or outcome-analysis results. As a result, no conclusion about the observed response pattern or its precision can be drawn from the registry record. This missing information should not be interpreted as evidence of either benefit or lack of benefit; the response results are simply not reported in the registry record.

The nonrandomized, unmasked, single-group classification is central to interpretation. The study does not provide a randomized control group for estimating a treatment contrast. The five tumor-defined groups are clinically and biologically distinct, so their outcomes cannot be treated as if participants had been assigned to comparable alternatives. A descriptive outcome in any one group would not, by itself, show what would have happened to those participants under another treatment.

Likewise, the safety counts describe events recorded among participants in the study groups, but they do not establish causation. There is no randomized comparator for estimating whether an event occurred more often because of the intervention. The posted safety summaries also do not give complete event-level context, including timing, duration, and attribution.

In general, interpreting a Phase II study requires both the observed outcome estimates and enough methodological detail to understand how participants were included and how missing assessments were handled. Those response results and analysis details are not reported in the registry record. The study's completion status and enrollment number do not substitute for those results. The defensible reading is therefore limited: the registry documents the design, response criteria, and selected safety summaries, while leaving the primary efficacy outcome unreported.

13. Why This Trial Matters Statistically

This trial illustrates why the registry design labels are important when interpreting outcomes. A nonrandomized, single-group study can document what was observed among treated participants, but it does not create a randomized comparison with an alternative treatment. That distinction remains important even when the registry separates participants into several tumor-defined groups: these groups are defined by different cancer types or molecular features, not by randomized allocation.

The study also makes clear that an endpoint definition and an endpoint result are different things. RECIST categories and lesion-change thresholds describe how response is to be classified. They do not reveal how many participants met those categories. Without posted counts and uncertainty estimates, readers cannot assess either the observed response distribution or its precision.

For biostatistical interpretation, the record highlights the value of reporting analysis populations, denominator rules, missing-data handling, and methods for any multiple group or outcome comparisons. These details help readers understand how an estimate was produced and what assumptions it relies on. They are not reported in the registry record, and no outcome analyses are posted.

The safety summaries also show the importance of distinguishing descriptive surveillance from comparative inference. Counts of participants affected by serious and other adverse events are useful as a record of what was reported, but they do not establish causal attribution or quantify differences against a control group. The selected serious-event terms offer additional descriptive context, while more detailed event-level information is not reported.

Overall, the statistical importance of this record lies in the gap between a specified outcome and a posted result, and in the consequences of a nonrandomized design for causal interpretation. Transparent outcome estimates, uncertainty measures, and analysis methods would be needed to support a fuller statistical assessment.

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 primary limitation for interpreting efficacy is that the registry record does not report response counts, rates, or uncertainty intervals. Although response is defined using RECIST categories, the observed outcome cannot be reconstructed from the definition alone. No response analysis entries are listed.

The study is nonrandomized, unmasked, and classified as single group. It therefore lacks a randomized comparator for estimating a treatment effect relative to another intervention. Its five groups are based on distinct tumor types or molecular features and should not be treated as exchangeable control arms. The number enrolled within each group is not reported in the registry record.

The record describes the drug as given orally at 125 mg QD on a 21-day schedule, but the schedule wording does not give further treatment details. The time-to-assessment schedule for RECIST responses is also not reported, despite a listed outcome timeframe of 10 years. Eligibility details, analysis populations, and the response-rate denominator are not specified in the available registry description.

Methods for handling participants without evaluable responses, missing data, multiplicity, and interim analyses are not reported in the registry record. The protocol sample-size justification is also not reported. These omissions prevent evaluation of how the planned enrollment, outcome analyses, and statistical assumptions were connected.

The adverse-event summaries are descriptive and do not establish drug causation. The registry does not give full event-level context, including timing, duration, attribution, and details of how events were assessed. Without a randomized control group, the summaries cannot estimate a comparative safety difference. These limitations constrain interpretation of both efficacy and safety, even though the study is marked completed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer — NCT01037790.
• Registry record last updated 2021-03-11; status last verified 2021-02.
• Results first posted 2021-03-11.
• 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

This completed Phase II trial evaluated PD-0332991 in five tumor-defined groups, with reported enrollment of 304. The registry classifies the study as nonrandomized, unmasked, and single group. The intervention is described as oral PD-0332991 at 125 mg QD on a 21-day schedule.

The primary outcome was response rate assessed using RECIST over a timeframe of 10 years. The record defines complete response, partial response, progressive disease, stable disease, and not evaluable, but does not report response counts, rates, or statistical analyses. It lists group-level serious and other adverse-event counts, deaths, and selected serious-event terms.

The nonrandomized design and distinct tumor-defined groups do not support a controlled treatment comparison. Analysis populations, missing-data procedures, multiplicity methods, and a protocol sample-size justification are not reported in the registry record. The posted information therefore describes the study design and selected safety summaries, while leaving the primary response results unavailable.