Gastric and Gastroesophageal Junction Cancer · Medical · Advanced / Metastatic · First-line HER2-negative advanced gastric/GEJ adenocarcinoma

RATIONALE-305

Clinical question: In first-line her2-negative advanced gastric/gej adenocarcinoma, does the investigational strategy improve clinically meaningful outcomes versus its control?

Registry: NCT03777657 · One underlying study; aliases and follow-up publications consolidated.

Phase III, double-blind, placebo-controlled RCT; 997 patients. Evidence cut-off: 13 November 2026.

Design, population and eligibility

Design / sample size

Phase III, double-blind, placebo-controlled RCT; 997 patients.

Eligibility

Previously untreated HER2-negative advanced gastric/GEJ adenocarcinoma.

Intervention

Tislelizumab + chemotherapy versus placebo + chemotherapy.

Tislelizumab 200 mg IV every 3 weeks with investigator-selected platinum/fluoropyrimidine chemotherapy.

Comparator

placebo + chemotherapy.

Primary endpoint: Co-primary OS in PD-L1 TAP ≥5% and ITT populations.

Key efficacy outcomes

ITT median OS 15.0 vs 12.9 months, HR 0.80 (95% CI 0.70–0.92), p=0.001. TAP ≥5% OS 17.2 vs 12.6 months, HR 0.74. At 3-year follow-up, ITT OS HR 0.79 and PFS HR 0.79; TAP ≥5% OS 16.4 vs 12.8 months, HR 0.71.

Reported outcome

15.0

Comparator: 12.9. The bars are a simple display of the first reported pair only; consult the endpoint and time horizon above.

Safety and treatment delivery

Grade ≥3 TRAEs 54% vs 50% in primary analysis; no new safety signals in 3-year follow-up.

Clinical interpretation and limitations

Positive phase III evidence. PD-L1 TAP is a tumour-area-positivity measure and must not be conflated with CPS; the thresholds are not interchangeable.

Interpret the reported hazard ratios in the context of the prespecified endpoint, statistical hierarchy, follow-up maturity, crossover/subsequent therapy and enrolled population. Median survival differences are not risk differences and must not be converted into NNT.

Absolute effect

No NNT/NNH is displayed unless an absolute event-risk difference at a clearly stated fixed timepoint can be calculated from reported trial data. Median survival differences and hazard ratios alone do not support an NNT. The visual above uses reported outcome data only.

Primary publication and follow-up

Primary publication

Registry / follow-up / authoritative source

Source-level verification status: primary publication identified and key quoted outcomes transcribed; where full-text toxicity or procedural details were not available, the page explicitly flags the limitation rather than inferring values.

Current-practice context · 13 November 2026

This page separates historical trial results from contemporary practice. Verify the applicable jurisdictional guideline, regulatory approval, biomarker assay, liver function, comorbidity and treatment availability before applying the evidence. NCCN Guidelines Insights are not a substitute for the full NCCN guideline.

Guideline/regulatory reconciliation and browser-rendered QA remain scheduled for the subsequent quality-control pass.