DESTINY-Gastric04
Trial question
What is the effect of trastuzumab deruxtecan in patients with HER2+ metastatic gastric cancer or GEJ adenocarcinoma who experienced disease progression after trastuzumab-based therapy?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
21.0% female
79.0% male
N = 494
494 patients (102 female, 392 male).
Inclusion criteria: patients with HER2+ metastatic gastric cancer or GEJ adenocarcinoma who experienced disease progression after trastuzumab-based therapy.
Key exclusion criteria: receipt of anti-cancer therapy after trastuzumab-containing treatment; MI in the past 6 months; symptomatic congestive HF; autoimmune, connective tissue, or inflammatory disorders where there is documented pulmonary involvement at the time of screening; prior complete pneumonectomy; multiple primary malignancies in the past 3 years.
Interventions
N=246 trastuzumab deruxtecan (at a dose of 6.4 mg/kg on day 1 of each 21-day cycle).
N=248 ramucirumab plus paclitaxel (ramucirumab 8 mg/kg on day 1 and 15 of each 28-day cycle plus paclitaxel 80 mg/m² of body-surface area on days 1, 8, and 15 of each 28-day cycle).
Primary outcome
Median overall survival
14.7 months
11.4 months
14.7 months
11.0 months
7.3 months
3.7 months
0.0 months
Trastuzumab
deruxtecan
Ramucirumab plus
paclitaxel
Significant
increase ▲
Significant increase in median overall survival (14.7 months vs. 11.4 months; HR 1.43, 95% CI 1.11 to 1.81).
Secondary outcomes
Significant increase in median progression-free survival (6.7 months vs. 5.6 months; HR 1.35, 95% CI 1.09 to 1.69).
Significant increase in confirmed objective response (44.3% vs. 29.1%; AD 15.1%, 95% CI 6.1 to 24.2).
Significant increase in disease control (91.9% vs. 75.9%; AD 16%, 95% CI 9.1 to 22.9).
Safety outcomes
No significant difference in drug-related adverse and serious adverse events.
Conclusion
In patients with HER2+ metastatic gastric cancer or GEJ adenocarcinoma who experienced disease progression after trastuzumab-based therapy, trastuzumab deruxtecan was superior to ramucirumab plus paclitaxel with respect to median overall survival.
Reference
Kohei Shitara, Eric Van Cutsem, Mahmut Gümüş et al. Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer. N Engl J Med. 2025 May 31. Online ahead of print.
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