Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial.
Jian Zhang, Quchang Ouyang, Qingyuan Zhang et al.
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In 30 seconds
This phase III, open-label, multicenter randomized trial compared trastuzumab botidotin with trastuzumab emtansine in adults with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane. Among 365 participants, blinded independent review found longer progression-free survival with trastuzumab botidotin: median 11.1 v 4.4 months (HR, 0.39 [95% CI, 0.30 to 0.51]; nominal P < .0001). Objective response was also more frequent. Overall survival data were immature, and grade ≥3 treatment-emergent adverse events occurred in 69.8% and 63.7%, respectively; ocular adverse events were common with botidotin.
Key findings
- Median progression-free survival was 11.1 v 4.4 months with trastuzumab botidotin versus trastuzumab emtansine (HR, 0.39 [95% CI, 0.30 to 0.51]; nominal P < .0001).
- Objective response rates were 76.9% (95% CI, 70.1 to 82.8) with botidotin and 53.0% (95% CI, 45.5 to 60.4) with emtansine.
- Grade ≥3 treatment-emergent adverse events occurred in 69.8% and 63.7%, respectively; ocular treatment-related events were frequent with botidotin, and most generally recovered or resolved with the protocol-defined algorithm.
- Overall survival was immature, with medians not reached in either group (HR, 0.62 [95% CI, 0.38 to 1.03]).
Why it matters
The trial reports a substantial progression-free survival advantage over an active comparator in previously treated HER2-positive advanced breast cancer, alongside a higher objective response rate. The findings also highlight a distinct toxicity profile: severe treatment-emergent events were common in both groups, and ocular events warrant attention with botidotin. Immature overall survival means the reported benefit is currently established for progression-free survival, not survival.
What to keep in mind
Follow-up was limited (median, 14.9 months), and overall survival data were immature. The open-label trial was conducted at 57 centers in China, which may limit generalizability.