DESTINY-Gastric04
After trastuzumab-based therapy, does trastuzumab deruxtecan improve outcomes over ramucirumab plus paclitaxel in HER2-positive gastric/GEJ cancer?
One underlying study; aliases and follow-up reports consolidated. Primary discipline: Medical.
494 patients with HER2-positive advanced gastric/GEJ adenocarcinoma previously treated with trastuzumab-based therapy.
HER2-positive disease after first-line trastuzumab-containing therapy; confirm HER2 status per trial/regulatory criteria.
494 (246 vs 248) randomised/evaluable as reported.
Trastuzumab deruxtecan 6.4 mg/kg IV every 3 weeks.
Ramucirumab 8 mg/kg days 1 and 15 plus paclitaxel 80 mg/m² days 1, 8, 15 every 28 days.
Endpoints and results
Primary OS; PFS, response and safety secondary.
- Median OS 14.7 vs 11.4 months; HR 0.70 (95% CI 0.55–0.90; p=0.0044).
- Median PFS 6.7 vs 5.6 months; HR 0.74 (95% CI 0.59–0.92; p=0.0074).
- ORR 44.3% vs 29.1%; grade ≥3 treatment-emergent AEs 68.0% vs 73.8%.
- Drug-related ILD/pneumonitis 13.9% vs 1.3%; one grade 3 event and no grade 4–5 events in cited analysis.
Absolute Effect and outcome visualisation
Median OS
months (median, not fixed-time rate) · Primary OS analysis. Bars compare reported medians only; they are not fixed-time survival probabilities.
Interpretation: No fixed-time OS rate reproduced here; NNT not calculated from the 3.3-month median OS difference.
Toxicity, discontinuation and quality of life
Trial-specific harms: ILD/pneumonitis is a distinctive potentially serious harm; grade ≥3 treatment-emergent AEs 68.0% vs 73.8%.
Treatment burden/discontinuation: Every-three-week ADC dosing requires pulmonary symptom monitoring and prompt evaluation for suspected ILD.
Quality of life: No numeric QoL advantage claimed without the PRO report.
Subgroups, maturity and limitations
Subgroups: Applies to HER2-positive disease after trastuzumab-based treatment; reassess HER2 status when clinically appropriate.
Maturity: Phase III report published 2025; follow-up continues.
Limitations: Confirm exact article DOI and fixed-time survival rates during freshness audit; source link currently points to PubMed query.
DESTINY-Gastric04 showed improved OS and response over ramucirumab–paclitaxel in second-line HER2-positive gastric/GEJ cancer; ILD remains a critical harm.
Use current regional guidelines, patient fitness, biomarkers, competing risks, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.
Primary sources and registry
Registry: NCT04704934
The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.