Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.

Name: Αlpha¹ Rigor Record — Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.
Item: Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.
Rating: 96
Author: Αlpha¹

Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Sakamoto Y, Nishina T, Inaki K, Kuwahara Y, Wada N, Suto F, Arita T, Sugihara M, Tsuchihashi Z, Saito K, Kojima A, Yamaguchi K

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Αlpha¹ Rigor Review — 3★ (Adequate), 0 critical, 4 high issues for “Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 16, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

3 / 5

Adequate — real issues to address

Observational Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★

Model-reported confidence: highReviewer agreement: moderateEngine: 7.39.0Source: full text

Not verified in this report

Statistics were not checked: no recomputable values were found in this text — no test statistic reported with its degrees of freedom, no effect estimate printed with both a 95% CI and a p-value, and no percentage printed with both its count and its denominator.

Problems surfaced4 types

Numerical inconsistencies1

Values 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.

Internal contradictions in the reported numbersAssessed

Overstated conclusions3

Conclusions 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.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions only partially backed by the presented evidenceAssessed

This Αlpha¹ Rigor Review uses AI 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-conducted exploratory biomarker analysis of a randomized phase 2 trial, with strong reporting of ethics, key resources, and data availability. The main weaknesses are the lack of pre-specified analysis plans, multiple testing correction, and some imprecise p-value reporting, which are typical of exploratory analyses.

All three reviewers classified the study as observational (exploratory biomarker analysis of a randomized trial); no divergence. The statistics component recomputed 0 tests (none had test statistic + df or effect + CI), so no statistical claims are verified; the citation component found no retracted or unresolved references; the reproducibility check found 2 live links.

11 major claims checked against the paper's own evidence: 3 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

2 integrity concerns flagged (0 high).

Reporting

Eight Dimensions8 pass

The introduction cites prior clinical trials (DESTINY-Gastric01, DESTINY-Gastric02) and discusses spatial/temporal heterogeneity of HER2 in gastric cancer, providing a rationale for exploring biomarkers. It acknowledges gaps in knowledge (e.g., 'Specific biomarkers related to therapeutic response have not been explored extensively'). The objective is clearly stated: to identify patients who may benefit based on biomarkers. Limitations of prior work are implicitly addressed by focusing on exploratory biomarker analyses.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior work on T-DXd, HER2 heterogeneity, and ctDNA biomarkers, and logically links these to the study objectives.

Evidence

direct quote[Introduction, paragraph 1-3]

“Spatial heterogeneity (heterogeneous HER2 expression and concomitant alterations) and temporal heterogeneity (loss of HER2 expression and acquired alterations) may make it challenging to identify patients with gastric or GEJ cancer who have the potential to respond to T-DXd treatment.”