Sequencing trastuzumab deruxtecan and sacituzumab govitecan in metastatic breast cancer: a systematic review and meta-analysis.
Antonios Katsarolis, Maria Anastasiou, Abraham Pouliakis et al.
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In 30 seconds
This systematic review and meta-analysis assessed whether treatment order affects outcomes when patients with metastatic breast cancer receive both trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG). It included 17 retrospective studies; seven contributed to the progression-free survival on the second antibody-drug conjugate (PFS2) analysis. The pooled hazard ratio for T-DXd→SG versus SG→T-DXd was 1.54 (95% CI 0.98-2.40; I²=61%). Median PFS2 was 3.3 months with SG→T-DXd and 2.8 months with T-DXd→SG. Although point estimates favoured SG→T-DXd, the evidence does not establish that either sequence is superior.
Key findings
- Seven studies contributed to the PFS2 meta-analysis, including 292 patients treated SG→T-DXd and 286 treated T-DXd→SG.
- The pooled HR for T-DXd→SG versus SG→T-DXd was 1.54 (95% CI 0.98-2.40; I²=61%).
- Median PFS2 was 3.3 months with SG→T-DXd and 2.8 months with T-DXd→SG.
- After excluding one study, the pooled HR was 1.72 (95% CI 1.23-2.41; I²=10%); with covariate-adjusted estimates, it was 1.36 (95% CI 0.89-2.10).
Why it matters
Both ADCs may be treatment options for patients with metastatic breast cancer, including those with HER2-low disease, yet the preferred order is uncertain. This synthesis suggests a possible advantage for SG followed by T-DXd, but the estimates are inconsistent across analyses and the authors rate certainty as very low. The findings highlight the need to interpret apparent sequencing differences cautiously.
What to keep in mind
All 17 included studies were retrospective, and the authors note likely confounding by tumour subtype. The evidence was rated very low certainty, with heterogeneity in the primary pooled analysis.