This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01] (NCT03329690), a randomized phase 2 study. The primary outcome is Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03329690 |
| Phase | Phase 2 |
| Condition | Neoplasm, Gastrointestinal |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 233 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Daiichi Sankyo Co., Ltd. |
| Results posted | Yes |
2. Clinical Question
Population
The randomized comparison concerned participants with HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma whose disease had progressed on two prior regimens. Those regimens included a fluoropyrimidine agent, a platinum agent, and trastuzumab. The primary outcome population is described as the Primary Cohort in the Intent-to-Treat Analysis Set. The arm descriptions specify HER2 status as IHC 3+ or IHC 2+/ISH+.
Intervention
Participants assigned to DS-8201a received it once every 3 weeks. The primary endpoint was objective response assessed by independent central imaging review using RECIST version 1.1. The record also describes exploratory groups receiving DS-8201a, but those groups were non-randomized and are separate from the randomized comparison.
Comparator
The comparator was physician’s choice monotherapy prescribed before enrollment. The safety listings identify irinotecan and paclitaxel groups, as well as an overall physician’s choice group. The registry describes the study as randomized, open-label, and parallel; details of the randomization procedure are not reported in the registry record.
Primary question
The primary question was whether objective responses—complete response or partial response—were observed in the DS-8201a treatment cohort, as assessed by independent central review. The registry defines both confirmed and unconfirmed objective response rates. A single numerical response rate or treatment contrast, with an uncertainty interval or significance test, is not reported in the registry record.
3. Trial Design
DESTINY-Gastric01 is described as a Phase 2, multicenter, open-label, randomized, parallel study. Its official title identifies the population as people with HER2-expressing advanced gastric or gastroesophageal junction adenocarcinoma. The registry status is completed. The recorded study start was 2017-11-02, and the primary completion date was 2019-11-08. Enrollment is listed as 233, but the registry information summarized for the primary endpoint does not give group-level response counts or a numerical comparison.
The principal treatment comparison was DS-8201a versus physician’s choice monotherapy. DS-8201a was administered once every 3 weeks. Physician’s choice treatment was prescribed by the physician before enrollment. The randomized arm descriptions concern participants whose disease had progressed on two prior regimens and specify HER2 IHC 3+ or IHC 2+/ISH+ status. The study summary says the prior regimens included a fluoropyrimidine agent, a platinum agent, and trastuzumab.
The record also describes exploratory, non-randomized DS-8201a groups for HER2 IHC 2+/ISH- and HER2 IHC 1+ disease. These exploratory groups are not the randomized comparison and should not be combined conceptually with it. Their presence also means that the enrollment figure alone does not describe the population in the primary endpoint analysis. The primary endpoint population is stated to be the Primary Cohort in the Intent-to-Treat Analysis Set.
Open-label means masking was not used, according to the registry description; the record does not provide further detail about who knew treatment assignments or how that could have been handled during response assessment. Independent central imaging review was used for the primary response assessment, which provides an assessment distinct from investigator evaluation. The registry does not report the randomization method, allocation ratio, treatment adherence, or the statistical plan in the information summarized for this analysis.
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: In the Primary Cohort, participants with HER2 overexpressing gastric of GEJ adenocarcinoma were randomized (2:1) to either DS-8201a or physician's choice (irinotecan or paclitaxel). In the Exploratory Cohorts, participants with HER2 IHC 2+/ISH negative advanced gastric or GEJ adenocarcinoma who were naïve to HER2 treatment received DS-8201a.
Overall Study
| Stage | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|
| STARTED | 126 | 55 | 7 | 21 | 24 |
| Received Treatment | 125 | 55 | 7 | 20 | 24 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 126 | 55 | 7 | 21 | 24 |
Reasons for not completing this period:
| Reason | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|
| Progressive disease per RECIST | 85 | 44 | 6 | 16 | 20 |
| Clinical progression | 7 | 4 | 1 | 1 | 1 |
| Adverse Event | 22 | 4 | 0 | 1 | 2 |
| Death | 2 | 0 | 0 | 1 | 0 |
| Withdrawal by Subject | 2 | 3 | 0 | 1 | 0 |
| Physician Decision | 1 | 0 | 0 | 0 | 1 |
| Miscellaneous | 6 | 0 | 0 | 0 | 0 |
| Did not receive treatment | 1 | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Objective response rate was assessed in the Primary Cohort in the Intent-to-Treat Analysis Set.
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: Baseline and demographic characteristics were assessed in the Full Analysis Set.
| Characteristic | Unit | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 125 | 55 | 7 | 20 | 24 | 231 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 55 | 24 | 3 | 11 | 17 | 110 |
| Age, Categorical: >=65 years | Participants | 70 | 31 | 4 | 9 | 7 | 121 |
| Age, Continuous | years | 64.2 (SD 10.36) | 64.9 (SD 10.54) | 63.4 (SD 8.96) | 62.5 (SD 10.87) | 55.5 (SD 12.12) | 63.3 (SD 10.86) |
| Sex: Female, Male: Female | Participants | 30 | 13 | 2 | 4 | 7 | 56 |
| Sex: Female, Male: Male | Participants | 95 | 42 | 5 | 16 | 17 | 175 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 125 | 55 | 7 | 20 | 24 | 231 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: South Korea | participants | 26 | 11 | 1 | 4 | 5 | 47 |
| Region of Enrollment: Japan | participants | 99 | 44 | 6 | 16 | 19 | 184 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set), measured over Baseline to date of first documented objective response (CR or PR), up to 36 months postdose.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with an objective response, assessed by independent central imaging review in the Intent-to-Treat Analysis Set. Objective response means achieving a best overall response of complete response or partial response. Under the registry’s RECIST version 1.1 definitions, complete response requires disappearance of all target lesions; partial response requires at least a 30% decrease in the sum of target-lesion diameters. The stated assessment window runs from baseline to the date of first documented objective response, up to 36 months postdose.
The endpoint is useful because it translates changes in measurable disease into a response category. In general, response endpoints can provide a direct description of tumor shrinkage among the population being assessed. Independent central review offers an assessment separate from the treating investigator’s judgment. It does not, by itself, establish how long a response lasts or whether survival differs; the registry lists duration of response and overall survival among secondary outcomes.
The registry reports confirmed and unconfirmed objective response rates as separate concepts. Confirmation distinguishes responses that meet the registry’s confirmation criterion from those that are not confirmed. The numerical rates, counts, uncertainty intervals, and a single comparative estimate are not reported in the registry record. Therefore, the endpoint definition can be described, but the magnitude and precision of the observed primary response result cannot be characterized from the information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies objective response as the primary outcome, but the available record does not provide the response counts or percentages for the randomized groups. It also does not provide a numerical treatment contrast, confidence interval, or p-value for that outcome. Consequently, the posted information does not support a quantitative statement about the size or precision of a difference in objective response between DS-8201a and physician’s choice. The endpoint’s definition is clear, but a definition is not a result.
The endpoint includes both confirmed and unconfirmed response rates. These represent distinct ways of describing response status, so a single number should not be inferred by selecting one without the corresponding result and analysis details. The record’s primary endpoint population is the Primary Cohort in the Intent-to-Treat Analysis Set. Results from the exploratory HER2 groups or from investigator assessment would not automatically answer the primary randomized comparison; those populations or assessment methods differ.
The registry lists 233 as enrollment. That figure should not be treated as the number assessed for the primary endpoint, nor as the denominator in either randomized treatment group. Group-specific analysis denominators and response counts are not reported in the registry record. Without those quantities, response percentages cannot be independently checked or interpreted in relation to the analysis population.
Confidence intervals are a general statistical way to express uncertainty around an estimated result. A narrower interval indicates greater precision under the method used, while a wider interval indicates more uncertainty. No primary-endpoint interval is reported in the registry information summarized for this analysis, so precision cannot be judged numerically. Likewise, no test result or prespecified threshold for interpreting a difference is reported. A lack of a reported estimate is not evidence that the groups had equal outcomes; it means the registry record does not furnish the result needed to assess that question.
Safety information is available as event counts and percentages for listed groups, but it should be read separately from the primary efficacy endpoint. Serious adverse events, other adverse events, and deaths are distinct listings and do not substitute for a comparative response analysis. The record includes exploratory groups and physician’s choice subgroups in its safety listing, including groups with different numbers at risk. Those group-level counts should not be combined to create a new total or treated as randomized efficacy comparisons. The most defensible interpretation is therefore limited: the registry describes the study design, primary response definition, and selected safety summaries, while the numerical primary response comparison and its uncertainty are not reported in the registry record.
9. Statistical Methods Explained
Objective response is a binary outcome at the participant level: a participant either meets the response definition or does not. The registry defines response as complete response or partial response under RECIST version 1.1, assessed by independent central imaging review. Complete response requires disappearance of all target lesions, while partial response requires at least a 30% decrease in the sum of target-lesion diameters. The recorded endpoint is a percentage, but the registry information does not give the response counts or percentages needed to inspect that calculation.
What does independent central review contribute?
As a general statistical and measurement principle, independent review can separate outcome assessment from the treating clinician’s assessment. This is relevant in an open-label study because treatment assignment is not masked. Central review does not eliminate every possible source of measurement variation, and the registry information does not describe the review process in detail. Investigator-assessed response is separately named among secondary outcomes, underscoring that assessment source is part of the endpoint definition and should be kept clear when interpreting results.
Why are confirmed and unconfirmed response distinct?
The record reports that both confirmed and unconfirmed objective response rates are considered. In general, confirmation requirements distinguish a response that is subsequently verified under the study’s assessment rules from one that is not confirmed. This can make the definition more stringent, but the precise confirmation schedule and operational details are not reported in the registry record. The two response categories should not be treated as interchangeable, and their results should be read with the corresponding definition and analysis population. Their numerical results are not reported.
What can a confidence interval tell the reader?
In general, a confidence interval expresses the sampling uncertainty around an estimated quantity under a specified statistical method. For a response percentage, it gives a range of values compatible with the observed data and method; for a difference between groups, an interval can show both the estimated direction and its precision. The registry information summarized for the primary endpoint does not include a response estimate, group contrast, or confidence interval. No numerical assessment of precision can therefore be made from the record.
Why does the analysis population matter?
The registry states that the primary response endpoint was assessed in the Primary Cohort in the Intent-to-Treat Analysis Set. In general, an intent-to-treat analysis uses the randomized assignment as the basis for grouping participants, preserving the comparison established by randomization even when treatment received or follow-up differs. The exact implementation, handling of participants without evaluable response assessments, and endpoint-specific denominators are not reported in the registry record. The stated population should not be confused with the overall enrollment figure or with the exploratory non-randomized groups.
What does the planning illustration represent?
General sample-size planning uses assumptions about the treatment contrast, variability, significance level, allocation, and desired power to estimate how many participants or events may be needed in a future study. Such a calculation is a planning illustration, not an observed result and not a measure of the power achieved by this completed trial. The planning assumptions described for this analysis use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. The specific numerical planning outputs are not reported in the registry record. They should not be mistaken for the trial’s original design justification, which is not reported in the registry record.
For binary outcomes, planning quantities are expressed as participants per arm. These planning estimates depend on the effect chosen for detection; changing that assumed effect changes the required sample size. This is a general property of statistical design, not evidence about the trial’s observed response result. No observed-power conclusion can be drawn from a planning illustration. The registry information does not report the original sample-size justification, the planned statistical test, or the treatment-effect assumptions used when the study was designed.
More broadly, interpretation requires the estimate, its uncertainty, the analysis population, and the method used to handle incomplete outcome data. A response percentage without its denominator would be difficult to evaluate, and a comparison without an interval would leave precision unclear. Here, the registry defines the endpoint and analysis population but does not report the numerical primary result, its uncertainty, or sufficient details to reproduce the analysis. Any further statistical conclusions about the primary outcome would go beyond what is reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 17 outcome measures, including overall survival, progression-free survival, duration of response, disease control, objective response assessed by different reviewers, time to treatment failure, and pharmacokinetic measures. It also lists one analysis entry. The information summarized for this analysis does not describe a multiplicity strategy for interpreting several outcomes or several response definitions. Whether hypotheses were ordered, adjusted, or designated as exploratory beyond the descriptions in the registry is not reported in the registry record.
Multiplicity matters in general because examining several outcomes or comparisons can increase the chance of finding an apparently notable result by chance. Adjustment methods and hierarchical testing can address this concern, but no such method should be assumed without documentation. The record also does not report interim analyses or a stopping rule. This absence of detail does not establish that no such procedures existed; it means they are not reported in the registry record.
The primary outcome population is stated as the Primary Cohort in the Intent-to-Treat Analysis Set. The registry information does not explain how missing response assessments, withdrawals, or participants without an evaluable scan were handled. It does not report endpoint-specific denominators or an imputation method. These details matter because missing outcome data can affect both the estimated response percentage and the comparability of groups. The exact analysis implementation is not reported in the registry record.
The record’s stated analysis population should be kept distinct from enrollment and from the exploratory non-randomized groups. No additional assumptions about exclusions, missingness, or the statistical plan can be made from the stated population label alone. The original sample-size justification is also not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| DS-8201a | 58 | 125 | 46.4% |
| Physician's Choice Irinotecan | 15 | 55 | 27.3% |
| Physician's Choice Paclitaxel | 1 | 7 | 14.3% |
| Physician's Choice Overall | 16 | 62 | 25.8% |
| Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | 6 | 20 | 30.0% |
| Exploratory: Naïve HER2 IHC 1+, DS-8201a | 11 | 24 | 45.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| DS-8201a | 98 of 125 |
| Physician's Choice Irinotecan | 46 of 55 |
| Physician's Choice Paclitaxel | 4 of 7 |
| Physician's Choice Overall | 50 of 62 |
| Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | 16 of 20 |
| Exploratory: Naïve HER2 IHC 1+, DS-8201a | 21 of 24 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| DS-8201a | 125 of 125 |
| Physician's Choice Irinotecan | 54 of 55 |
| Physician's Choice Paclitaxel | 7 of 7 |
| Physician's Choice Overall | 61 of 62 |
| Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | 20 of 20 |
| Exploratory: Naïve HER2 IHC 1+, DS-8201a | 24 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|---|
| Decreased appetite | Metabolism and nutrition disorders | 13 of 125 | 1 of 55 | 0 of 7 | 1 of 62 | 2 of 20 | 4 of 24 |
| Disease progression | General disorders | 3 of 125 | 2 of 55 | 0 of 7 | 2 of 62 | 2 of 20 | 0 of 24 |
| Anaemia | Blood and lymphatic system disorders | 4 of 125 | 2 of 55 | 0 of 7 | 2 of 62 | 0 of 20 | 0 of 24 |
| Jaundice cholestatic | Hepatobiliary disorders | 3 of 125 | 1 of 55 | 0 of 7 | 1 of 62 | 1 of 20 | 1 of 24 |
| Cholangitis | Hepatobiliary disorders | 3 of 125 | 1 of 55 | 0 of 7 | 1 of 62 | 0 of 20 | 1 of 24 |
| Pyrexia | General disorders | 3 of 125 | 1 of 55 | 0 of 7 | 1 of 62 | 0 of 20 | 1 of 24 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 5 of 125 | 0 of 55 | 0 of 7 | 0 of 62 | 0 of 20 | 0 of 24 |
| Hydronephrosis | Renal and urinary disorders | 1 of 125 | 1 of 55 | 0 of 7 | 1 of 62 | 1 of 20 | 1 of 24 |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 125 | 0 of 55 | 1 of 7 | 1 of 62 | 0 of 20 | 0 of 24 |
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 125 | 1 of 55 | 0 of 7 | 1 of 62 | 1 of 20 | 0 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 79 of 125 | 27 of 55 | 2 of 7 | 29 of 62 | 11 of 20 | 19 of 24 |
| Decreased appetite | Metabolism and nutrition disorders | 76 of 125 | 27 of 55 | 1 of 7 | 28 of 62 | 13 of 20 | 18 of 24 |
| Neutrophil count decreased | Investigations | 79 of 125 | 18 of 55 | 3 of 7 | 21 of 62 | 8 of 20 | 12 of 24 |
| Anaemia | Blood and lymphatic system disorders | 71 of 125 | 17 of 55 | 2 of 7 | 19 of 62 | 10 of 20 | 11 of 24 |
| White blood cell count decreased | Investigations | 49 of 125 | 18 of 55 | 3 of 7 | 21 of 62 | 4 of 20 | 7 of 24 |
| Diarrhoea | Gastrointestinal disorders | 41 of 125 | 20 of 55 | 0 of 7 | 20 of 62 | 6 of 20 | 8 of 24 |
| Malaise | General disorders | 44 of 125 | 9 of 55 | 1 of 7 | 10 of 62 | 4 of 20 | 9 of 24 |
| Constipation | Gastrointestinal disorders | 31 of 125 | 13 of 55 | 2 of 7 | 15 of 62 | 5 of 20 | 5 of 24 |
| Fatigue | General disorders | 27 of 125 | 15 of 55 | 0 of 7 | 15 of 62 | 5 of 20 | 6 of 24 |
| Platelet count decreased | Investigations | 48 of 125 | 4 of 55 | 0 of 7 | 4 of 62 | 3 of 20 | 7 of 24 |
Serious events with the highest arm-level rate: decreased appetite (16.7%), neoplasm progression (14.3%), disease progression (10.0%), gastric haemorrhage (8.3%), pneumonia bacterial (5.0%).
The safety listing separates serious adverse events, other adverse events, and deaths. For DS-8201a, 58 of 125 participants at risk are listed as affected by a serious adverse event; 125 of 125 are listed as affected by other adverse events, and 98 deaths are reported. For physician’s choice overall, 16 of 62 are listed with serious adverse events, 61 of 62 with other adverse events, and 50 deaths. The physician’s choice subgroups are listed separately: the irinotecan group has 15 of 55 with serious adverse events, 54 of 55 with other adverse events, and 46 deaths; the paclitaxel group has 1 of 7 with serious adverse events, 7 of 7 with other adverse events, and 4 deaths.
The registry also lists serious-event terms with percentages, including decreased appetite at 16.7%, neoplasm progression at 14.3%, disease progression at 10.0%, gastric haemorrhage at 8.3%, pneumonia bacterial at 5.0%, and tumour pain at 5.0%. The record does not specify a denominator for those term percentages in the information, so they should not be converted into counts.
As a general principle, serious and severe are not synonymous: seriousness describes regulatory criteria, while severity describes intensity. The event counts do not by themselves establish that treatment caused an event. These safety summaries are descriptive; no causal interpretation or formal comparative safety analysis is reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry establishes that DESTINY-Gastric01 was a randomized Phase 2 comparison of DS-8201a and physician’s choice for the stated HER2-expressing advanced gastric or gastroesophageal junction adenocarcinoma population. It defines objective response, identifies independent central review, and specifies the primary analysis population. These details clarify what the primary endpoint was intended to measure and which cohort it concerned.
The registry information does not include a numerical primary response result. It therefore cannot establish the response rate in either randomized group, the size or direction of a treatment difference, or how precise an estimate might be. It also cannot support a conclusion that the treatments had equal or different response outcomes. The missing estimate should not be interpreted as a zero effect or as evidence of no effect.
Nor does the endpoint definition alone answer questions about durability, survival, or the balance of benefits and harms. The registry names overall survival, progression-free survival, duration of response, and other outcomes among secondary measures, but their numerical results are not reported in the information. Safety listings provide counts and selected event percentages, but descriptive event counts do not establish causation or provide a complete comparative assessment.
General statistical interpretation requires matching a result to its population, endpoint definition, assessment method, and uncertainty. Here, the population and measurement definition are described, but the primary estimate, denominators, confidence interval, and test result are not reported in the registry record. Accordingly, the appropriate conclusion is limited to what the record documents: the study design and outcome definitions are available, while the quantitative primary efficacy result cannot be evaluated from the reported information.
13. Why This Trial Matters Statistically
This study is statistically notable for pairing randomization with an open-label design and an independently reviewed primary imaging endpoint. Randomization is intended, in general, to create comparable groups at assignment; central review offers an outcome assessment separate from the treating investigator’s judgment. These design features address different parts of the evidence process and do not remove the need to report estimates, denominators, and uncertainty.
The population definition is also important. The randomized arm descriptions focus on HER2-overexpressing disease after progression on two prior regimens, while the registry separately describes exploratory non-randomized HER2 groups. Keeping those populations distinct is essential when assessing what a treatment comparison can answer. The overall enrollment figure does not by itself disclose the primary analysis denominators or the results for the randomized groups.
For clinical researchers, the record illustrates why a clearly specified endpoint is not enough for statistical interpretation. RECIST version 1.1 definitions and independent central review explain how response was classified, but the magnitude and precision of a comparison require the actual outcome data and analysis. The registry’s separate confirmed and unconfirmed response definitions further show why the endpoint version must accompany any reported estimate.
The record also demonstrates the value of transparent reporting of missing-data rules, multiplicity handling, analysis methods, and sample-size rationale. Those details are not reported in the registry information. Their absence limits the conclusions that can be drawn without implying that a particular method was or was not used. The most informative statistical reading distinguishes documented design features from unreported analytical details and avoids converting a described study question into a claim about its outcome.
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 main limitation for interpreting the primary endpoint is that the registry information gives its definition and population but not response counts, group percentages, a treatment contrast, a confidence interval, or a p-value. The primary result’s magnitude and precision therefore cannot be assessed. The endpoint description includes confirmed and unconfirmed response, but the numerical values for either are not reported in the registry record.
Group-specific denominators for the primary efficacy analysis are also not reported. Enrollment is listed as 233, but it should not be used as a denominator for a treatment group or as a substitute for the primary analysis population. The primary endpoint is assigned to the Primary Cohort in the Intent-to-Treat Analysis Set; further details about inclusion, evaluability, and missing response assessments are not reported in the registry record.
The study is open-label, and details about masking of assessors beyond the statement that independent central review was used are not reported. The randomization procedure and allocation ratio are also not reported in the registry record. These gaps do not establish a flaw in the study, but they limit assessment of how the design was implemented.
Although safety counts and selected serious-event percentages are listed, the information does not supply a complete account of exposure time, event timing, or causal attribution. The denominator for the serious-event term percentages is not reported in the information. The record also does not report the multiplicity approach, missing-data method, interim-analysis procedures, original sample-size justification, or detailed statistical test. These limitations constrain independent evaluation and should not be filled with assumptions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01] — NCT03329690.
- Registry record last updated 2022-03-18; status last verified 2022-03.
- Results first posted 2020-11-27.
- 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.
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18. Record Summary
DESTINY-Gastric01 (NCT03329690) is a completed, randomized, open-label, parallel Phase 2 study of DS-8201a and physician’s choice treatment in HER2-expressing advanced gastric or gastroesophageal junction adenocarcinoma. The record lists enrollment as 233, with a study start of 2017-11-02 and primary completion on 2019-11-08. The primary endpoint is the percentage of participants with objective response assessed by independent central review under RECIST version 1.1, in the Primary Cohort of the Intent-to-Treat Analysis Set.
The registry defines complete and partial response and states that confirmed and unconfirmed response rates are reported. A numerical primary response result and comparative estimate are not reported in the registry record. The record also describes secondary outcomes, exploratory non-randomized groups, and safety listings. Details of the original sample-size justification, missing-data handling, multiplicity strategy, and primary statistical analysis are not reported in the registry record.