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Promising drug, underwhelming results: The phase 2 TALENT trial found that trastuzumab deruxtecan (T-DXd) showed only modest benefit as neoadjuvant therapy in HER2-low, hormone receptor-positive early breast cancer. Pathologic complete response rates were low across all three treatment arms — 7% with T-DXd alone, 3% with T-DXd plus anastrozole, and 9% when sequenced with chemotherapy. Adding endocrine therapy or chemotherapy offered little meaningful improvement.
Promising drug, underwhelming results in early breast cancer
The phase 2 TALENT trial, presented at ESMO Congress 2026, tested trastuzumab deruxtecan (T-DXd) as a neoadjuvant treatment in patients with stage II–III HER2-low, hormone receptor-positive (HR+) breast cancer. Researchers evaluated T-DXd alone, in combination with anastrozole, and sequenced with chemotherapy — but none of the approaches delivered impressive pathologic complete response (pCR) rates.
Notably, no patients achieved pCR with just 6 cycles of T-DXd; responses only emerged when cycles were extended to 8. The sequential arm (T-DXd followed by chemotherapy) also came with a higher burden of serious adverse events, including two cases of interstitial lung disease.
By the Numbers
Why it matters: T-DXd has shown strong results in metastatic HER2-low breast cancer, raising hopes for its use earlier in the disease course. These TALENT findings suggest it may not be the neoadjuvant game-changer clinicians were hoping for — prompting a rethink of optimal treatment sequencing in this patient population.
