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 The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer (NCT03581786), a randomized phase 3 study. The primary outcome is IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03581786 |
| Phase | Phase 3 |
| Condition | Recurrent or Metastatic NPC |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 289 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Shanghai Junshi Bioscience Co., Ltd. |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with recurrent or metastatic nasopharyngeal cancer. The registry summary describes first-line treatment and requires histological or cytological confirmation. It describes the primary endpoint as applying to all patients. The registry record does not provide further detail about the population used in the posted endpoint analysis.
Intervention
The intervention was toripalimab injection, identified as JS001, combined with gemcitabine and cisplatin. The registry description specifies toripalimab at 240 mg every three weeks. Gemcitabine was given on Days 1 and 8, and cisplatin on Day 1 of each cycle. Chemotherapy was planned for up to 6 cycles and toripalimab for up to 2 years.
Comparator
The comparator was placebo combined with the same chemotherapy. The registry describes placebo at 240 mg every three weeks, chemotherapy on the same schedule as in the toripalimab arm, and placebo for up to 2 years. The comparison therefore isolates the added study drug against placebo while retaining the chemotherapy regimen in both arms.
Primary question
The primary question was whether toripalimab plus chemotherapy differed from placebo plus chemotherapy in IRC-assessed progression-free survival according to RECIST v1.1. The posted endpoint is the median duration in months, with a 95% confidence interval where reported. The registry does not post a hazard ratio or a sponsor-reported statistical comparison for this endpoint.
3. Trial Design
This was a phase III, randomized, placebo-controlled, multicenter, double-blind, parallel-group study. The registry lists quadruple masking. The summary describes random assignment in a 1:1 ratio. Enrollment is recorded as 289, with 143 participants in the placebo-plus-chemotherapy arm and 146 in the toripalimab-plus-chemotherapy arm. These are the arm counts listed with the posted outcomes.
Both groups received gemcitabine and cisplatin. The registry describes gemcitabine 1000 mg/m² intravenously on Days 1 and 8 and cisplatin 80 mg/m² intravenously on Day 1 of each cycle, given every three weeks for up to 6 cycles. The study drug or placebo was administered before chemotherapy on the same three-week schedule. The record describes toripalimab or placebo as continuing for up to 2 years.
The trial started on 2018-10-18, reached primary completion on 2020-05-30, and is listed as completed. The registry summary identifies the primary endpoint as progression-free survival in all patients. It also lists overall survival and response-related outcomes among the secondary outcomes. The registry record does not report the details needed to reconstruct the randomization procedure, concealment process, masking roles, or operational conduct beyond its design labels and treatment descriptions.
The listed enrollment and arm counts describe trial participation, not necessarily the number included in every endpoint analysis. Endpoint-specific analysis populations, exclusions, and missing-data handling are not reported in the registry record. The posted arm counts should therefore be read as the counts associated with the outcomes, rather than as proof that every participant contributed complete information at every assessment.
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
| Stage | Placebo Combine With Chemotherapy | TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy |
|---|---|---|
| STARTED | 143 | 146 |
| COMPLETED | 67 | 89 |
| NOT COMPLETED | 76 | 57 |
Reasons for not completing this period:
| Reason | Placebo Combine With Chemotherapy | TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy |
|---|---|---|
| Death | 67 | 47 |
| Withdrawal by Subject | 2 | 5 |
| Lost to Follow-up | 7 | 4 |
| reason other than specified above | 0 | 1 |
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.
| Characteristic | Unit | Placebo Combine With Chemotherapy | TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy | Total |
|---|---|---|---|---|
| Participants analysed | 143 | 146 | 289 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 136 | 139 | 275 |
| Age, Categorical: >=65 years | Participants | 7 | 7 | 14 |
| Age, Continuous | years | 49.68 (SD 10.355) | 45.84 (SD 11.26) | 47.74 (SD 10.973) |
| Sex: Female, Male: Female | Participants | 27 | 22 | 49 |
| Sex: Female, Male: Male | Participants | 116 | 124 | 240 |
| Race/Ethnicity, Customized: Asian | Participants | 143 | 146 | 289 |
| Region of Enrollment: Singapore | participants | 2 | 3 | 5 |
| Region of Enrollment: China | participants | 134 | 136 | 270 |
| Region of Enrollment: Taiwan | participants | 7 | 7 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as IRC-assessed Progression-Free Survival (PFS) According to RECIST v1.1, measured over up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival measures the time from the relevant starting point until disease progression or death, subject to the trial’s analysis rules. The primary endpoint was IRC-assessed progression-free survival using RECIST v1.1. IRC assessment means the endpoint was evaluated by an independent review committee, rather than relying only on investigator assessment. The registry specifies a timeframe of up to 2 years.
The registry’s progression definition includes a relative increase in the sum of target-lesion diameters of at least 20%, with an absolute increase of at least 5 mm from the smallest on-study sum, or the appearance of one or more new lesions. These criteria give a specified basis for identifying progression in the recorded endpoint.
A median is the point by which half of the observed time-to-event distribution has reached an event, under the analysis method used. It is a summary of the group’s distribution, not a prediction of an individual participant’s course. A confidence interval conveys uncertainty around the estimated median. In general, progression-free survival is used to summarize disease control over time, while accounting for the timing of events; the registry record does not describe the detailed censoring or estimation procedures used for this analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted median progression-free survival was 8.2 months in the placebo-plus-chemotherapy arm, with a 95% confidence interval of 7.03 to 9.79 months. In the toripalimab-plus-chemotherapy arm, the posted median was 21.4 months; the lower confidence limit was 11.73 months, and the upper limit is not reported in the registry record. The arm-level medians are numerically different, with the longer median in the toripalimab arm.
Those medians describe each arm separately. They do not by themselves quantify the relative rate of progression or death between arms, and they do not give a complete inferential comparison. A hazard ratio and its confidence interval are not reported in the registry record. Nor is a sponsor-reported p-value or other primary-endpoint comparison reported. The missing upper confidence limit in the toripalimab arm also means the interval for that median cannot be fully read from the registry entry.
The secondary outcomes offer additional, but distinct, views of response and disease control. Investigator-assessed objective response was 75.5% (95% CI 67.64 to 82.32) with placebo plus chemotherapy and 82.2% (95% CI 75.01 to 88.02) with toripalimab plus chemotherapy. The unadjusted recalculated comparison has p = 0.165. Investigator-assessed disease control was 90.9% (95% CI 84.96 to 95.07) and 91.1% (95% CI 85.26 to 95.17), respectively; its unadjusted recalculated comparison has p = 0.956. These results do not provide the primary endpoint’s time-to-event comparison.
The one-year investigator-assessed progression-free survival rates were 26.2% (95% CI 18.96 to 33.99) and 61.4% (95% CI 52.28 to 69.27), respectively. The unadjusted recalculated comparison has p < 0.001. This result is directionally consistent with the arm-level primary medians, but it remains a secondary outcome and is not a substitute for the sponsor’s primary analysis. The registry lists 0 reported analyses, and these recalculated comparisons should be understood as supplementary, unadjusted summaries rather than registry-reported sponsor analyses.
Confidence intervals communicate uncertainty in estimates; they are not guarantees that the true value lies within the displayed limits. A p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It does not measure the size or clinical importance of an effect. Because the record does not describe multiplicity control, the secondary p-values should not be treated as confirmatory evidence on their own.
9. Statistical Methods Explained
The posted primary outcome is a time-to-event measure, reported as a median and confidence interval. The registry also provides selected binary secondary outcomes, such as response rates and the proportion progression-free at a specified time. These types of outcomes answer different statistical questions: a median summarizes the timing of events, while a percentage summarizes the proportion meeting an outcome definition.
What does a median time-to-event estimate mean?
In general, a time-to-event analysis uses both the timing of observed events and information from participants whose event time is not observed during follow-up. Such participants may be censored under the analysis rules. A median is estimated from the distribution of event times; it is not simply an arithmetic average of observed durations. The registry does not report the specific method used to estimate the primary median, how censoring was handled, or the analysis cutoff for the posted result. Those details are important for assessing how the estimate was constructed.
The registry posts an arm-specific median for each group, but no primary hazard ratio or sponsor-reported comparison. In general, a hazard ratio summarizes the relative event rate over follow-up under assumptions about how that relative rate behaves. It is not the same quantity as a ratio of medians. The registry does not report the hazard ratio, its confidence interval, or the sponsor’s primary inferential result, so the medians alone cannot establish the estimated relative event rate or its uncertainty.
How should the confidence intervals be read?
In general, a confidence interval expresses the precision of an estimate under the method used to calculate it. A wider interval indicates less precision than a narrower interval, all else being equal. The placebo arm’s median is reported with limits of 7.03 and 9.79 months. For the toripalimab arm, the lower limit is 11.73 months, but the upper limit is not reported in the registry record. The displayed information therefore does not give a complete confidence interval for that arm. A comparison of separate arm-level intervals is not a replacement for a confidence interval calculated directly for the treatment contrast.
For binary outcomes, the posted percentages are arm-specific estimates with confidence intervals. The recalculated comparisons use unadjusted differences in proportions and p-values. These are simple summary-statistic comparisons, not the sponsor’s reported analyses. An unadjusted comparison does not account for possible prespecified analysis choices or multiplicity across outcomes. The registry does not report the statistical methods behind a sponsor analysis for these outcomes.
Why can over-dispersion matter?
As a general statistical point, over-dispersion occurs when the variability in data exceeds what a statistical model assumes. If a model does not allow for that extra variability, standard errors can be too small and confidence intervals can be too narrow. This is a general consideration in statistical modeling; the registry record does not report whether over-dispersion was assessed or whether it was relevant to any of the analyses posted for this trial.
The sample-size illustrations are planning exercises based on the observed effect, not evidence about the trial’s achieved power. Their stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect set to a fraction of the observed effect. For binary outcomes, the illustrations are expressed as participants per arm for 80% power or 90% power. They do not show how the trial was actually designed, and the sample-size justification is not reported in the registry record. A planning calculation based on an observed result is especially dependent on that result and should not be mistaken for a prospective design assumption.
The registry indicates that values are missing or not estimable for a two-arm comparison of the median time endpoint. This is consistent with the absence of a posted primary contrast, but the record does not explain why the comparison is unavailable. The primary result should therefore be read as arm-specific medians and reported limits, not as a complete statistical comparison of treatment groups.
What cannot be concluded from these summaries?
General statistical interpretation distinguishes an estimate from the method and assumptions that produced it. The arm-level medians and percentages describe the posted data. Without the full analysis specification, participant-level data, and sponsor-reported primary result, it is not possible to independently verify endpoint derivation, censoring, covariate adjustment, handling of missing observations, or robustness to alternative assumptions. These are not claims that a particular method was or was not used; the details are simply not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, including overall survival, response, duration of response, disease control, and additional progression-free survival measures. It also lists 23 outcome measures and 0 reported analyses. The record does not state how the primary and secondary hypotheses were ordered, whether a gatekeeping procedure was planned, or whether p-values were adjusted for testing multiple outcomes. Without that information, the secondary p-values should be treated as unadjusted exploratory comparisons rather than as results with a documented family-wise error plan.
Missing-data handling is not reported in the registry record. In a time-to-event analysis, the treatment of participants without an observed event depends on censoring and follow-up rules. For binary outcomes, the handling of participants with missing or unevaluable assessments can affect the denominator and estimate. The registry provides arm counts alongside the posted results but does not explain whether all randomized participants were included in each endpoint analysis, how missing assessments were classified, or whether any sensitivity analyses were conducted.
The analysis populations are likewise not described in sufficient detail to identify whether the posted results use an intention-to-treat population, a modified population, or another prespecified set. The primary outcome description refers to all patients, but the specific operational definition and any exclusions are not reported in the registry record. No interim analysis plan, stopping rule, or detailed statistical analysis plan is reported. These absences limit assessment of the statistical framework; they do not establish that such procedures were absent from the trial, only that they are 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 |
|---|---|---|---|
| Placebo Combine With Chemotherapy | 62 | 143 | 43.4% |
| TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy | 64 | 146 | 43.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo Combine With Chemotherapy | 67 of 143 |
| TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy | 47 of 146 |
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 |
|---|---|
| Placebo Combine With Chemotherapy | 143 of 143 |
| TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy | 146 of 146 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo Combine With Chemotherapy | TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy |
|---|---|---|---|
| Blood and lymphatic system disorders | Blood and lymphatic system disorders | 39 of 143 | 39 of 146 |
| Infections and infestations | Infections and infestations | 10 of 143 | 19 of 146 |
| Metabolism and nutrition disorders | Metabolism and nutrition disorders | 5 of 143 | 7 of 146 |
| General disorders and administration site | General disorders | 5 of 143 | 5 of 146 |
| Hepatobiliary disorders | Hepatobiliary disorders | 4 of 143 | 5 of 146 |
| Gastrointestinal disorders | Gastrointestinal disorders | 2 of 143 | 6 of 146 |
| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | 3 of 143 | 4 of 146 |
| Nervous system disorders | Nervous system disorders | 3 of 143 | 4 of 146 |
| Skin and subcutaneous tissue | Skin and subcutaneous tissue disorders | 2 of 143 | 4 of 146 |
| Investigations | Investigations | 3 of 143 | 1 of 146 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo Combine With Chemotherapy | TORIPALIMAB INJECTION(JS001 )Combine With Chemotherapy |
|---|---|---|---|
| Blood and lymphatic system disorders | Blood and lymphatic system disorders | 142 of 143 | 143 of 146 |
| Gastrointestinal disorders | Gastrointestinal disorders | 138 of 143 | 135 of 146 |
| Metabolism and nutrition disorders | Metabolism and nutrition disorders | 118 of 143 | 116 of 146 |
| General disorders and administration site conditions | General disorders | 91 of 143 | 89 of 146 |
| Investigations | Investigations | 91 of 143 | 88 of 146 |
| Nervous system disorders | Nervous system disorders | 78 of 143 | 84 of 146 |
| Respiratory, thoracic and mediastinal disorders Cough | Respiratory, thoracic and mediastinal disorders | 71 of 143 | 69 of 146 |
| Skin and subcutaneous tissue disorders | Skin and subcutaneous tissue disorders | 50 of 143 | 68 of 146 |
| Infections and infestations | Infections and infestations | 38 of 143 | 62 of 146 |
| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | 40 of 143 | 43 of 146 |
Serious events with the highest arm-level rate: blood and lymphatic system disorders (27.3%), infections and infestations (13.0%), metabolism and nutrition disorders (4.8%), gastrointestinal disorders (4.1%), general disorders and administration site (3.5%).
The registry records serious adverse events in 62 of 143 participants in the placebo-plus-chemotherapy arm and 64 of 146 participants in the toripalimab-plus-chemotherapy arm. It records deaths in 67 participants and 47 participants, respectively. These are counts reported for the listed groups. The registry entry does not provide enough detail in these figures alone to determine timing, attribution, causes of death, exposure-adjusted rates, or whether events overlapped within participants.
The listed serious-event categories include blood and lymphatic system disorders at 27.3%, infections and infestations at 13.0%, metabolism and nutrition disorders at 4.8%, gastrointestinal disorders at 4.1%, general disorders and administration site conditions at 3.5%, and hepatobiliary disorders at 3.4%. The registry record does not specify the denominator or arm assignment for these category percentages in the registry record for interpretation, so they should not be used to infer a between-arm comparison.
The counts describe safety events recorded in the registry; they do not by themselves establish that a study drug caused an event or that one regimen is safer. The record also lists any adverse event for all participants in each arm, but provides no additional breakdown in these figures. Further definitions and analysis details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The results establish what was posted for this trial: the median progression-free survival was 8.2 months with placebo plus chemotherapy and 21.4 months with toripalimab plus chemotherapy. The record gives a 95% confidence interval for the placebo-arm median and a lower confidence limit for the toripalimab-arm median, but does not report the latter’s upper limit. The registry does not provide a primary hazard ratio or sponsor-reported test of the between-arm difference.
The numerical difference between arm medians is not, by itself, a complete estimate of the treatment effect. Medians do not describe the full distribution of event times, and the posted arm-level summaries do not show how the relative difference behaved over follow-up. They also do not tell a reader what outcome an individual participant would experience. The secondary results add context but remain distinct endpoints, with the registry lacking a reported multiplicity plan and sponsor analyses.
Randomization and placebo control are important design features for comparing groups, but interpretation still depends on the analysis population, outcome ascertainment, follow-up, missingness, and statistical methods. Several of those details are not reported in the registry record. The registry summaries alone therefore do not support a full appraisal of the prespecified analysis or its assumptions.
The safety counts should also be interpreted as recorded event counts rather than causal conclusions. The available information does not provide event-level timing, attribution, or detailed comparisons by exposure. These results do not establish that an event was caused by toripalimab, placebo, or chemotherapy.
In short, the posted summaries show a longer arm-level median and a marked separation in the one-year investigator-assessed progression-free survival rates, alongside less separated response and disease-control summaries. They do not supply the primary comparative estimate needed to quantify uncertainty around the treatment contrast. A larger observed median is not a guarantee of benefit for an individual, nor does it answer questions the registry does not report.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint summary and a treatment comparison are not interchangeable. The registry posts median progression-free survival separately by arm, but not the primary hazard ratio or the sponsor’s inferential comparison. Readers can describe the observed medians, yet cannot recover the full primary comparison from those values alone. A time-to-event endpoint depends on event timing and censoring, while a median compresses that distribution into a single summary.
The record also highlights the distinction between primary and secondary outcomes. The secondary results include proportions and a fixed-time progression-free survival rate, which can provide complementary descriptions of response and disease control. Their meaning depends on endpoint definitions, assessment processes, analysis populations, and multiplicity handling. The record does not report the sponsor’s analyses or a multiplicity strategy, so unadjusted secondary comparisons have limited confirmatory value.
Planning illustrations based on observed effects should not be confused with prospective design justification or observed power. They describe hypothetical sample sizes under stated assumptions. They cannot show whether the trial was designed around a clinically meaningful effect, because the design justification is not reported in the registry record.
For biostatistical reading, the important questions are therefore not only what the arm-specific estimates are, but also how the estimand was defined, how incomplete follow-up was treated, which population was analyzed, and how uncertainty in the contrast was quantified. Those details are not reported in the registry record. The distinction between posted descriptive results and a complete prespecified analysis is central to interpreting what these data can support.
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 most important limitation for interpreting the primary endpoint is the absence of a reported between-arm hazard ratio, confidence interval for that contrast, or sponsor-reported statistical test. The registry posts medians by arm, but the upper confidence limit for the toripalimab-arm median is not reported. The median summaries consequently give an incomplete account of comparative uncertainty.
Analysis details are limited. The registry does not report the analysis population definition, censoring rules, missing-data approach, statistical model, covariate adjustments, or sensitivity analyses. It describes the primary outcome as IRC-assessed and identifies RECIST v1.1, but does not provide further detail about the assessment process or endpoint derivation. These gaps restrict independent assessment of the analysis.
For the secondary outcomes, the record lists multiple measures but does not report a multiplicity strategy or sponsor analyses. The unadjusted recalculated comparisons should therefore be interpreted cautiously and not treated as definitive evidence across outcomes. The available posted secondary results also do not cover every secondary outcome listed in the registry.
The safety summaries are counts and category percentages with limited context. The registry information used does not specify category denominators, event attribution, exposure-adjusted rates, or detailed timing. These limitations prevent a complete comparative safety interpretation from the figures alone.
Finally, the sample-size illustrations use observed effects and stated simplifying assumptions; they are not the trial’s design justification or observed power. The registry record does not report the planned sample-size rationale. These trial-specific reporting limitations do not imply that the unreported methods were not used, but they do constrain what can be verified from the registry entry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Efficacy and Safety Study of TORIPALIMAB INJECTION Combined With Chemotherapy for Nasophapyngeal Cancer — NCT03581786.
- Registry record last updated 2025-09-02; status last verified 2024-08.
- Results first posted 2022-04-18.
- 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
The registry describes a phase III randomized, placebo-controlled, multicenter, double-blind study of toripalimab plus gemcitabine and cisplatin versus placebo plus the same chemotherapy for recurrent or metastatic nasopharyngeal cancer. Enrollment is listed as 289. The primary outcome is IRC-assessed progression-free survival according to RECIST v1.1, reported as median time in months.
The posted medians are 8.2 months for placebo plus chemotherapy and 21.4 months for toripalimab plus chemotherapy. The registry does not report a complete confidence interval for the toripalimab-arm median or a sponsor-reported primary comparison. Selected secondary and safety results are also posted, but multiplicity, missing-data, and analysis-population details are not reported in the registry record.