ESMO Congress 2026

T-DXd (trastuzumab deruxtecan) belongs to the anti-HER2 antibody-drug conjugate (ADC) class. As for the evidence already established for this asset, the usable information in the current materials comes from the on-site discussants: several experts used T-DXd's success in the metastatic breast cancer setting as the reference background, and debated from there whether that benefit can be extrapolated to early-stage disease. Regarding key published phase III trials of ADCs in the same class, the background references provided this time all belong to other fields such as psychology, statistical methodology, and sports science, containing no anti-HER2 ADC or breast cancer trial data; such prior evidence is pending confirmation in these materials and is therefore not elaborated here.

At ESMO26, Sara Hurvitz presented the final results of the TALENT trial (LBA23): three neoadjuvant strategies in HR+/HER2-low early breast cancer — T-DXd alone (6-8 cycles), T-DXd plus anastrozole, and T-DXd x 4 cycles followed by sequential TC chemotherapy x 4. The key numbers: pCR was 7%, 3%, and 9%, respectively; RCB 0/1 was 16%, 17%, and 17%, respectively. Despite an overall response rate (ORR) of about 66%, pCR remained very low, and per the live posts, there were no pCRs without 8 cycles. The authors concluded the benefit was "modest," while one commenter called it "disappointing." Another post noted that higher baseline HER2 protein levels may be associated with higher pCR rates.

Relative to prior knowledge, the step TALENT advances lies in answering three questions: first, adding endocrine therapy (anastrozole) to T-DXd did not improve pCR (3% vs 7% for monotherapy); second, sequencing TC chemotherapy brought only marginal improvement (9%); third, the contrast between high ORR and low pCR again confirms that pCR is a limited surrogate endpoint in HR+ disease, a point emphasized by multiple discussants. In the discussion session, Barbara Pistilli placed TALENT in the context of three trials of ADCs sharing the same target, linker and payload class, noting that its low pCR rate is comparable to NACT and other ADCs in HR+/HER2- early breast cancer. Some on-site commentary called this "probably first negative trial" for T-DXd, but sample size and statistical design details were not disclosed in the posts, so that characterization awaits confirmation.

As for limitations, the materials here are only live conference posts, with no sample size, study design, or survival follow-up data disclosed; on safety, discussants explicitly raised the need to weigh efficacy, ILD risk, and treatment positioning in early disease, but specific safety figures were not given in the posts. Given the inherent heterogeneity of HER2-low disease, the overall judgment from attendees is that these results do not support T-DXd as an alternative to standard neoadjuvant chemotherapy in HR+/HER2-low early breast cancer, and whether it can move from metastatic benefit to curative-intent early treatment still requires more evidence.