ADCs Transforming Early-Stage HER2-Positive Care

This segment introduces the rapidly evolving role of antibody-drug conjugates (ADCs) in early-stage HER2-positive breast cancer, highlighting how emerging data may shift both neoadjuvant and adjuvant treatment strategies. Recent trials, including DESTINY-Breast05 and DESTINY-Breast11, suggest that trastuzumab deruxtecan (T-DXd) may challenge long-standing standards of care.

In the adjuvant setting, DESTINY-Breast05 compared T-DXd with ado-trastuzumab emtansine (T-DM1) for patients with residual disease after neoadjuvant therapy. Early results demonstrate improved disease-free survival with T-DXd, although the study population consisted of very high-risk patients, such as those with residual nodal disease or initially inoperable tumors. Careful patient selection will therefore be essential when translating these findings into practice. Safety considerations are also critical, particularly the risk of interstitial lung disease (ILD), which occurred in approximately 10% of patients and requires close monitoring, especially in the curative-intent setting.

In the neoadjuvant setting, DESTINY-Breast11 evaluated T-DXd–based therapy in high-risk disease and showed significantly higher pathologic complete response (pCR) rates compared with standard regimens. Notably, pCR exceeded 60% in hormone receptor–positive disease and 80% in hormone receptor–negative disease. The regimen also demonstrated favorable tolerability, with lower rates of cardiotoxicity, neutropenia, and ILD than expected.

These findings raise important clinical questions regarding optimal sequencing and postoperative management when T-DXd is used earlier in the disease course. ADCs have the potential to redefine curative-intent treatment, although thoughtful risk–benefit assessment and implementation strategies are needed.