Standard chemoradiotherapy with concurrent and adjuvant camrelizumab in patients with high risk nasopharyngeal carcinoma: multicentre, randomised, open label, phase 3 trial.
You R, Xu GQ, Ding X, Liang JH, Liu ZG, Zou X, Liu YP, Hu GY, Liu YM, Duan CY, Liu LZ, Zhang WJ, Liu Q, Li HF, Ouyang YF, Duan XT, Wang Q, Peng L, Liang JL, Feng ZK, Qin ZH, Liu X, He ZK, Zhang B, Long GX, Jiang YH, Lei F, Huang PY, Hua YJ, Chen MY
- DOI
- 10.1136/bmj-2025-085863
- Record issued
- 2026-08-10
- Engine
- 7.29.0
- Exported
- 2026-09-21
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/913b0eab-bd66-4d59-8999-843f4177812f is authoritative.
How this rating was calculated
- ReportingKey resources partially met−0.25★
- ReportingData & code availability partially met−0.25★
- References were not verified against Crossref/OpenAlex.
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
This is a well-designed, well-reported phase 3 RCT of camrelizumab plus chemoradiotherapy in high-risk nasopharyngeal carcinoma, with strong reporting of randomisation, ethics, statistics, and transparency (trial registration, CONSORT, limitations, proportional conclusions), and open Dryad data deposition. The main weaknesses are minor reporting gaps: investigational product manufacturers are not stated, analysis code is only in supplemental files rather than a version-controlled repository, and race/ethnicity is not explicitly reported. Copyedit issues are minor typos, including a stray reference appended to the Dryad DOI.
Both independent reviewers agreed on all eight dimension statuses (6 pass, 2 warn) and identical overall scores; the only sub-criterion divergence was how to label the demographics gap (reported but inadequate vs not reported), which does not change the dimension status. Statistics verification recomputed only 4 tests (those with test statistic + df or effect estimate + CI); threshold-only and resampling-based p-values were not machine-verifiable, so the paper's statistics beyond those 4 checks remain unverified rather than confirmed. Citations, claim audit, and integrity checks raised no findings.
Numerical inconsistencies
None foundValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
Checked — nothing surfaced.
Recomputed 4 tests: 4 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 3 via agent-written checks.
- CONSISTENTreported p = .001 · recomputed p = .001Recomputed hazard ratio 0.51 (95% CI 0.34–0.77), reported p=0.001
“hazard ratio 0.51, 95% confidence interval 0.34 to 0.77, P=0.001”
Taken as given: 0.34–0.77 is a two-sided 95% confidence interval for the hazard ratio of 0.51, not a range, an IQR, or a different interval level; the hazard ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.001 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(0.51, 0.34, 0.77, 1) - CONSISTENTreported p = .020 · recomputed p = .019Reviewers 1, 2Recompute the two-sided p-value for distant metastasis-free survival hazard ratio from its 95% CI
“stratified hazard ratio for distant metastasis or death 0.54, 95% CI 0.32 to 0.90”
Taken as given: the 0.54 is the hazard ratio and 0.32-0.90 its two-sided 95% CI for distant metastasis-free survival; the CI is a two-sided 95% interval; the reported p-value is two-tailed; the log hazard ratio is approximately normally distributedMethod: Two-sided p derived from the log hazard ratio and its 95% CI using a normal approximation (pCI, log=1).How we recomputed it: pCI(0.54, 0.32, 0.90, 1) - CONSISTENTreported p = .001 · recomputed p = .002Reviewer 1Recompute the two-sided p-value for locoregional recurrence-free survival hazard ratio from its 95% CI
“stratified hazard ratio for locoregional relapse or death 0.38, 95% CI 0.21 to 0.70”
Taken as given: the 0.38 is the hazard ratio and 0.21-0.70 its two-sided 95% CI for locoregional recurrence-free survival; the CI is a two-sided 95% interval; the reported p-value is two-tailed; the log hazard ratio is approximately normally distributedMethod: Two-sided p derived from the log hazard ratio and its 95% CI using a normal approximation (pCI, log=1).How we recomputed it: pCI(0.38, 0.21, 0.70, 1) - CONSISTENTreported p = .190 · recomputed p = .184Reviewers 1, 2Recompute the two-sided p-value for overall survival hazard ratio from its 95% CI
“stratified hazard ratio for death 0.59, 95% CI 0.27 to 1.28”
Taken as given: the 0.59 is the hazard ratio and 0.27-1.28 its two-sided 95% CI for overall survival; the CI is a two-sided 95% interval; the reported p-value is two-tailed; the log hazard ratio is approximately normally distributedMethod: Two-sided p derived from the log hazard ratio and its 95% CI using a normal approximation (pCI, log=1).How we recomputed it: pCI(0.59, 0.27, 1.28, 1)
Overstated conclusions
1 finding · worst lowConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Conclusions only partially backed by the presented evidenceAssessed
6 major claims checked against the paper's own evidence: all adequately supported.
- partialReviewers 1, 2This study validates the precision treatment concept of using dynamic imaging assessment and Epstein-Barr virus DNA changes to individualise subsequent treatment intensity in nasopharyngeal carcinoma.The study demonstrates the feasibility of risk-stratifying by dynamic response, but 'validates' the broader precision-treatment concept is an interpretive extrapolation beyond the trial's primary endpoint.Evidence: The design used central imaging and EBV DNA testing to define a high-risk population and stratify treatment
This study validates the precision treatment concept of using dynamic imaging assessment and Epstein-Barr virus DNA changes to individualise subsequent treatment intensity in nasopharyngeal carcinoma.
Discussionreviewer’s wording - supportedReviewers 1, 2The addition of camrelizumab to concurrent chemoradiotherapy and as a maintenance treatment improved progression-free survival among patients with high risk nasopharyngeal carcinoma after induction chemotherapy.The primary endpoint analysis (HR 0.51, 95% CI 0.34-0.77, P=0.001) directly supports this claim.Evidence: 36-month PFS 83.4% v 71.3%; stratified hazard ratio 0.51 (0.34-0.77), P=0.001
“The addition of camrelizumab to concurrent chemoradiotherapy and as a maintenance treatment improved progression-free survival among patients with high risk nasopharyngeal carcinoma after induction chemotherapy.”
AbstractFind in source - supportedReviewer 1Camrelizumab concurrent with chemoradiotherapy and as a maintenance treatment showed a favourable safety profile.Reported grade 3-4 adverse events (50.5% vs 48.7%) and immune-related grade 3-4 events (10.2%) support a manageable safety profile.Evidence: Acute grade 3-4 AEs 50.5% vs 48.7%; immune-related grade 3-4 AEs in 19 patients (10.2%)
“Camrelizumab concurrent with chemoradiotherapy and as a maintenance treatment showed a favourable safety profile, with grade 3 or higher adverse events reported in 11% of patients.”
DiscussionFind in source - supportedReviewer 1Camrelizumab decreased the risk of local recurrence and distant metastasis.Secondary endpoint HRs for DMFS (0.54) and LRRFS (0.38) directly support this claim.Evidence: DMFS HR 0.54 (0.32-0.90); LRRFS HR 0.38 (0.21-0.70)
“Importantly, camrelizumab decreased the risk of local recurrence and distant metastasis, which reduced the medical costs and economic burden”
ResultsFind in source - supportedReviewer 2The addition of camrelizumab to concurrent chemoradiotherapy and as a maintenance treatment improved progression-free survival with a favourable safety profile.Safety profile is comparable between groups, with manageable immune-related events. Grade 3-4 acute AEs were 50.5% vs 48.7%, and immune-related AEs grade 3-4 occurred in 10.2% of patients.Evidence: Table 3: similar rates of AEs; immune-related AEs are reported only for the camrelizumab group.
“The incidence of acute and late adverse events (grade 3 or 4) was 50.5% and 3.2% in the camrelizumab group compared with 48.7% and 3.7% in the standard treatment group.”
ResultsFind in source - supportedReviewer 2Camrelizumab concurrent with chemoradiotherapy and as a maintenance treatment showed a favourable safety profile, with grade 3 or higher adverse events reported in 11% of patients.The paper reports grade 3 or higher immune-related adverse events in 10.2% of patients, and overall safety is comparable to the control group.Evidence: Table 3: immune-related adverse events grade 3-4: 19 patients (10.2%).
“Immunological adverse events (grade 3 or 4) occurred in 19 patients (10.2%) in the camrelizumab group.”
ResultsFind in source
Efficacy claim is anchored to an adequate endpoint and a meaningful effect.
- ADEQUATESurrogate endpointPrimary endpoint is progression-free survival, a clinical outcome (time to recurrence or death), not a surrogate.
“Progression-free survival was the primary endpoint, defined as the time from randomisation to the first documented evidence of disease recurrence (locoregional disease recurrence or distant metastasis) or death from any cause.”
- ADEQUATEEffect sizeHazard ratio 0.51 (95% CI 0.34 to 0.77) for progression-free survival, with 36-month rates 83.4% vs 71.3%, a 12.1% absolute difference. The paper explicitly states this is clinically meaningful.
“The three year progression-free survival rate was 83.4% (95% CI 78.3% to 88.8%) in the camrelizumab group compared with 71.3% (65.2% to 77.9%) in the standard treatment group (stratified hazard ratio for recurrence or death 0.51, 95% CI 0.34 to 0.77, P=0.001).”
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
2 findings · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
- Key resources under-identified (antibodies, cell lines, RRIDs)Assessed
The introduction cites multiple prior studies, including phase 3 trials of PD-1 inhibitors in NPC and the CONTINUUM study, establishing the rationale. The limitation of 20-30% recurrence despite intensified treatment is acknowledged, and the study addresses this by targeting a high-risk population defined by dynamic response to induction chemotherapy.
“several phase 3 trials have shown that adding programmed death 1 (PD-1) inhibitors to chemotherapy as first line treatment for recurrent or metastatic nasopharyngeal carcinoma provided statistically significantly and clinically meaningful benefits”
“patients with stage 2-3 disease without radiological or biological response after induction chemotherapy or with stage T4 or N3 disease regardless of the response status after induction chemotherapy can potentially be considered to be at high risk”
“Previous risk stratification tools largely focused on pretreatment factors such as staging based on imaging before treatment. However, considerable heterogeneity remains for most cancer subtypes”
“However, recurrence is observed in 20-30% of patients despite this intensified treatment approach, highlighting the need for new clinical modalities tailored to this high risk population.”
“Therefore, the addition of PD-1 inhibitors to the chemoradiotherapy regimen after induction chemotherapy may be a promising treatment strategy for this high risk population.”
“Previous risk stratification tools largely focused on pretreatment factors such as staging based on imaging before treatment. However, considerable heterogeneity remains for most cancer subtypes—patients with similar pretreatment staging may have different survival outcomes despite receiving the same treatment.”
Randomization used a centralized procedure with stratification by centre and stage, and block structure was concealed. The trial was open label but central imaging review was masked, and the open-label design is acknowledged as a limitation. A detailed power analysis was provided. Inclusion and exclusion criteria are clearly defined. The ITT analysis population is specified for efficacy, and the safety population is defined.
“The centralised randomisation procedure was conducted in the current study. Only the study coordinator and statistician knew the block structure, and they had no involvement in clinical aspects of the trial.”
“The treatment group assignment was known to the investigators and patients (open label), but this was masked to the central imaging review committee members”
“The power was 0.80 (1−β) and the two sided type I error (α) was 0.05. Based on a presumed 10% dropout rate, a total of 388 participants were estimated to be required”
“The centralised randomisation procedure was conducted in the current study. Only the study coordinator and statistician knew the block structure, and they had no involvement in clinical aspects of the trial.”
“The treatment group assignment was known to the investigators and patients (open label), but this was masked to the central imaging review committee members (W-JZ, L-ZL), who reviewed the imaging results of patients without access to information about treatment.”
“Based on a presumed 10% dropout rate, a total of 388 participants were estimated to be required (194 participants in each group), allowing for 98 events in the primary analysis of progression-free survival.”
Sex is reported in Table 1 (27.4% female, 72.6% male). Age is reported as median with IQR, and health status is reported via Karnofsky performance status. Race/ethnicity is not explicitly stated, but the study is set in China, which implies a predominantly Asian population. Demographics also include smoking, drinking, and family history.
“The population consisted of 107 women (27.4%) and 283 men (72.6%).”
“Age (years), median (IQR) | 46.0 (36.8-54.0) | 45.0 (35.0-54.0)”
“Female | 57 (29.4) | 50 (25.5)”
“Age (years), median (IQR) | 46.0 (36.8-54.0) | 45.0 (35.0-54.0)”
The study involves human participants, so irb_ethics_statement, informed_consent, and regulatory_compliance apply; iacuc_statement is not applicable. A named ethics body (Sun Yat-sen University Cancer Center IRB, protocol B2020-131-01) and each participating centre's ethics committee approved the study. Written informed consent is described. The trial conforms to the Declaration of Helsinki. All applicable criteria are adequate.
“The study was approved by the institutional review board of the Sun Yat-sen University Cancer Center (B2020-131-01) and respective ethics committee of each participating centre.”
“Eligibility assessment and obtaining written informed consent from eligible patients was the responsibility of investigators at each centre.”
“The trial conformed to the Declaration of Helsinki”
“The study was approved by the institutional review board of the Sun Yat-sen University Cancer Center (B2020-131-01) and respective ethics committee of each participating centre.”
“Eligibility assessment and obtaining written informed consent from eligible patients was the responsibility of investigators at each centre.”
Camrelizumab, cisplatin, and gemcitabine are named with doses and schedules, but no manufacturer or source is provided. Software (SPSS 25.0, R 4.4.1) is identified with version. Other sub-criteria (antibodies, cell lines, mycoplasma, organisms) are not applicable to this clinical trial.
“Patients in the camrelizumab group received 200 mg camrelizumab intravenously over a minimum duration of 60 minutes on the initial day of radiotherapy, once every three weeks for two cycles”
“Analyses were performed using SPSS software (version 25.0; IBM, Armonk, NY, USA) and R version 4.4.1.”
“Patients in the camrelizumab group received 200 mg camrelizumab intravenously over a minimum duration of 60 minutes on the initial day of radiotherapy, once every three weeks for two cycles during intensity modulated radiotherapy.”
“Analyses were performed using SPSS software (version 25.0; IBM, Armonk, NY, USA) and R version 4.4.1.”
Statistical tests are named (stratified log-rank, Cox proportional hazards, mixed effects model). The proportional hazards assumption was tested using Schoenfeld residuals. Exact p-values are reported (e.g., P=0.001). Hazard ratios with 95% CIs are provided for all survival endpoints. Software is identified. Data presentation includes Kaplan-Meier curves and per-group n. No arithmetic inconsistencies were detected.
“stratified hazard ratio for recurrence or death 0.51, 95% CI 0.34 to 0.77, P=0.001”
“Time-to-event data were visualised using Kaplan-Meier curves, and compared using the stratified log rank test.”
“the proportional hazards assumption was tested using Schoenfeld residuals.”
The data availability statement provides a concrete route to the data via Dryad (DOI). Code is mentioned as available in supplemental files, which does not meet the standard of a version-controlled public repository with a permanent identifier. No sequencing data were generated, so accession numbers are not applicable.
“The data underlying the findings in this paper are openly and publicly available in Dryad and can be found here: https://doi.org/10.5061/dryad.3j9kd51zg”
“The code used to analyse the data in the paper can be found in the supplemental files.”
“The data underlying the findings in this paper are openly and publicly available in Dryad and can be found here: https://doi.org/10.5061/dryad.3j9kd51zg”
“The code used to analyse the data in the paper can be found in the supplemental files.”
All seven applicable criteria are adequate: ClinicalTrials.gov registration (NCT04453826), CONSORT statement referenced, methods detailed enough to replicate, all outcomes reported including non-significant results (OS, QoL), dedicated limitations section, conclusions proportional (cautious about OS benefit needing longer follow-up), and detailed funding/COI.
“Additionally, this was an open label trial, which may have introduced biases that could be excluded in a double blind placebo controlled design.”
“Nevertheless, determining whether the 12% increase in progression-free survival at 36 months will translate into an overall survival benefit will require longer follow-up.”
“Trial registration ClinicalTrials.gov NCT04453826”
“the reporting of results was based on the CONSORT (consolidated standards of reporting trials) statement.”
“Additionally, this was an open label trial, which may have introduced biases that could be excluded in a double blind placebo controlled design.”
Registered (2 IDs: ClinicalTrials.gov). Reporting guideline cited: CONSORT.
Broken references and links
None foundReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Checked — nothing surfaced.
3 data/code links checked; 3 live.
- dataDryadLIVEHTTP 200https://doi.org/10.5061/dryad.3j9kd51zgResolves to Dryad (data repository).
- datahttps://clinicaltrials.gov/ct2/show/NCT04453826LIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://clinicaltrials.gov/ct2/show/NCT04448522LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
4 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 4 minor suggestions below.
4 copyedit issues flagged: mostly typo, other.
- MINORtypoDiscussion, Comparison with other studies“evaluated as having a radiologicaland biological response”→ Insert a space: "radiological and biological response"Missing space between 'radiological' and 'and'.
- MINORtypoDiscussion, Comparison with other studies“CONTINNUMM”→ Correct to "CONTINUUM"The study name is misspelled as 'CONTINNUMM' in multiple places.
- MINORtypoDiscussion, Comparison with other studies“ClinicalTrials.com, NCT04448522”→ Correct to "ClinicalTrials.gov"The registry name is written as 'ClinicalTrials.com' though the URL is correct.
- MINORotherData Availability Statement“https://doi.org/10.5061/dryad.3j9kd51zg (10.3322/caac.21834)”→ Remove the stray reference '(10.3322/caac.21834)'An unrelated citation appears appended to the Dryad DOI in the associated-data section.
The published work is methodologically robust and transparent; an informed reader should weigh the open-label design (acknowledged as a limitation) and the fact that only a subset of reported statistics was independently recomputed. No substantive erratum is warranted by the rigor findings; the minor copyedit issues — particularly the stray reference appended to the Dryad DOI in the data-availability statement and the 'ClinicalTrials.com' registry-name typo — could warrant a small correction, and the missing investigational-product sources and code repository are transparency gaps a reader should note.
- 1.HIGHrigorState the manufacturer/source of camrelizumab, cisplatin, and gemcitabine in the Methods/Procedures section.The investigational products are named with dose and regimen but not source, leaving the reagents_identified criterion incomplete (key_resources warn).
- 2.HIGHdata codeDeposit the analysis code in a version-controlled public repository (e.g., GitHub or Zenodo) with a permanent DOI and link to it in the Data availability statement.The code is currently only in supplemental files, which does not meet the standard of a version-controlled repository with a persistent identifier (data_code_availability warn).
- 3.HIGHreportingAdd explicit race/ethnicity (and comorbidity) information to Table 1 or the demographics section.These standard demographic fields are absent, which is a reporting gap for human-subjects research even though the study is set in a single-country Asian population.
- 4.MEDIUMdata codeRemove the stray reference '(10.3322/caac.21834)' appended to the Dryad DOI in the Data availability statement.An unrelated citation trails the data DOI and could mislead readers attempting to access the dataset.
- 5.MEDIUMcopyeditCorrect the trial name misspelling 'CONTINNUMM' to 'CONTINUUM' wherever it appears in the Discussion.A misspelled comparator-trial name undermines the credibility of the comparison and should be corrected.
- 6.MEDIUMcopyeditCorrect 'ClinicalTrials.com' to 'ClinicalTrials.gov' where the registry name is written out in the Discussion.The registry is ClinicalTrials.gov; the typo is inconsistent with the correct URL used elsewhere.
- 7.MEDIUMcopyeditFix the missing space in 'radiologicaland biological response' in the Discussion, Comparison with other studies.A typographical error that makes the sentence read incorrectly.
- 8.LOWreportingAdd a statement on how missing data were handled for the primary analysis (e.g., censoring rules in the survival analysis).Explicit missing-data handling strengthens the reporting of the analysis population and addresses the outlier/missing-data reporting criterion.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.