Efficacy and safety of trastuzumab deruxtecan in HER2-high and HER2-low breast cancer: a systematic review and meta-analysis of randomized controlled trials.
Sheng-Yen Hsiao, Wei-Ting Lin, Cheng-Yao Lin et al.
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In 30 seconds
This systematic review and random-effects meta-analysis pooled four randomized controlled trials involving 2,555 patients with HER2-high or HER2-low breast cancer to assess trastuzumab deruxtecan (T-DXd) against control regimens. T-DXd was associated with improved progression-free survival (HR = 0.433; 95% CI: 0.305-0.616; P < 0.001) and overall survival (HR = 0.720; 95% CI: 0.636-0.816; P < 0.001), with benefits reported across HER2 subgroups. Treatment also increased several adverse events, notably interstitial lung disease and decreased left ventricular ejection fraction.
Key findings
- Progression-free survival favored T-DXd over control regimens (HR = 0.433; 95% CI: 0.305-0.616; P < 0.001; I 2 = 90.7%).
- Overall survival favored T-DXd (HR = 0.720; 95% CI: 0.636-0.816; P < 0.001; I 2 = 0%).
- Interstitial lung disease risk was higher with T-DXd (RR = 13.832; P < 0.001), as was decreased left ventricular ejection fraction (RR = 2.247; P < 0.001).
- Anemia, nausea, vomiting, decreased appetite, and alopecia increased; neutropenia and diarrhea risks were comparable between groups.
Why it matters
The pooled randomized-trial evidence indicates survival benefits with T-DXd across HER2-high and HER2-low subgroups, while also identifying clinically relevant toxicities. These findings help frame the balance between treatment benefit and adverse-event burden when considering evidence for this therapy, particularly the need to remain alert to pulmonary and cardiac safety signals.
What to keep in mind
Progression-free survival results showed substantial heterogeneity (I 2 = 90.7%), indicating variability across the included trials.