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Bending the Curve Trial by Trial
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DESTINY-Gastric04

Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)

Phase 3N = 494NCT04704934

Population
HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma confirmed on tumour biopsy taken after progression on trastuzumab-based therapy.
Design
International randomised phase 3 trial comparing second-line trastuzumab deruxtecan 6.4 mg/kg with ramucirumab plus paclitaxel. Primary endpoint: overall survival. Secondary endpoints included progression-free survival, confirmed objective response, disease control, duration of response and safety. 494 patients were randomised. The paper does not carry the trial name in its title.
Primary endpoint
OS
Arms
  • Ramucirumab plus paclitaxel (control): Ramucirumab plus paclitaxel
  • Trastuzumab deruxtecan (experimental): Trastuzumab deruxtecan 6.4 mg per kilogram of body weight
People
Shitara K, DESTINY-Gastric04 Trial Investigators
OSHR 0.70 (95% CI 0.55–0.90)Δ median OS+3.3 monthsPFSHR 0.74 (95% CI 0.59–0.92)Δ ORR+15.2 points
Show the numbers
Results reported for DESTINY-Gastric04
EndpointAnalysisTrastuzumab deruxtecanRamucirumab plus paclitaxelEffect
OSRandomised patients (494)primaryShitara 2025median 14.7 monthsmedian 11.4 monthsHR 0.70 (95% CI 0.55–0.90)P=0.004
PFSRandomised patients (494)primaryShitara 2025——HR 0.74 (95% CI 0.59–0.92)Secondary endpoint; the abstract does not give medians.
ORRRandomised patients (494)Confirmed objective response (complete or partial response lasting 4 weeks or more)primaryShitara 202544.3%29.1%Secondary endpoint. Adjudicated drug-related interstitial lung disease or pneumonitis: 13.9% with trastuzumab deruxtecan (grade 1 or 2 in 33 patients, grade 3 in 1) and 1.3% with ramucirumab plus paclitaxel (grade 3 in 2, grade 5 in 1). Drug-related adverse events of grade 3 or higher: 50.0% versus 54.1%.
Results reported for DESTINY-Gastric04
EndpointAnalysisTrastuzumab deruxtecanRamucirumab plus paclitaxelEffect
OSRandomised patients (494)primaryShitara 2025median 14.7 monthsmedian 11.4 monthsHR 0.70 (95% CI 0.55–0.90)P=0.004
PFSRandomised patients (494)primaryShitara 2025——HR 0.74 (95% CI 0.59–0.92)Secondary endpoint; the abstract does not give medians.
ORRRandomised patients (494)Confirmed objective response (complete or partial response lasting 4 weeks or more)primaryShitara 202544.3%29.1%Secondary endpoint. Adjudicated drug-related interstitial lung disease or pneumonitis: 13.9% with trastuzumab deruxtecan (grade 1 or 2 in 33 patients, grade 3 in 1) and 1.3% with ramucirumab plus paclitaxel (grade 3 in 2, grade 5 in 1). Drug-related adverse events of grade 3 or higher: 50.0% versus 54.1%.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.70.55–0.9
PFS0.740.59–0.92
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0102030Months (modelled)
  • Trastuzumab deruxtecan (experimental)
  • Ramucirumab plus paclitaxel (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsTrastuzumab deruxtecanRamucirumab plus paclitaxel
0100.0%100.0%
965.4%57.9%
1842.8%33.5%
2826.7%18.2%
3717.5%10.5%
Primary publication: Shitara K, Van Cutsem E, Gümüş M, Lonardi S, de la Fouchardière C, Coutzac C, et al. Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer. N Engl J Med. 2025;393(4):336-348. PubMedDOI

Appears in

Sources

  1. Shitara K, Van Cutsem E, Gümüş M, Lonardi S, de la Fouchardière C, Coutzac C, et al. Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer. N Engl J Med. 2025;393(4):336-348.

    PubMedDOI