Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-positive advanced or metastatic gastric or gastroesophageal cancer: a meta-analysis of single-arm trials.
Akhil Deepak Vatvani, Gilbert Lazarus, Reyad Al Jabiri et al.
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In 30 seconds
This systematic review and random-effects meta-analysis pooled prospective single-arm trials of trastuzumab deruxtecan (T-DXd) in HER2-positive advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. Eight trials included 1,182 patients; 77.9% received treatment in the second-line or later setting. The pooled objective response rate was 42.7% (95% CI 36.9-48.6), and the disease control rate was 82.4% (95% CI 78.6-86.0). Grade ≥ 3 adverse events occurred in 46.7% (95% CI 32.5-61.2), while interstitial lung disease occurred in 2.1% (95% CI 0.2-5.6).
Key findings
- Across eight trials and 1,182 patients, pooled objective response rate was 42.7% (95% CI 36.9-48.6).
- Pooled disease control rate was 82.4% (95% CI 78.6-86.0).
- Grade ≥ 3 adverse events occurred in 46.7% (95% CI 32.5-61.2); interstitial lung disease occurred in 2.1% (95% CI 0.2-5.6).
- Pooled overall survival was 54.5% (95% CI 43.5-65.3) and progression-free survival was 73.4% (95% CI 60.5-84.5), with substantial heterogeneity.
Why it matters
The pooled results summarize antitumor activity and toxicity across prospective studies in a population largely treated after first-line therapy. The response and disease-control estimates provide useful context for evaluating T-DXd, while the frequency of severe adverse events and the reported interstitial lung disease signal underscore the importance of weighing potential benefit against toxicity.
What to keep in mind
All included trials were single-arm, so the pooled estimates do not establish comparative benefit. Heterogeneity was substantial for several outcomes, including overall survival, progression-free survival, and grade ≥ 3 adverse events.