Recent trials highlight T-DXd's superior efficacy and manageable toxicity in treating high-risk HER2-positive breast cancer, reshaping treatment strategies.
Early findings from DESTINY-Breast05 and DESTINY-Breast11 suggest encouraging activity for T-DXd in high-risk early HER2-positive breast cancer, with signals of deeper responses in both neoadjuvant and adjuvant settings. Many clinicians are now weighing whether to incorporate T-DXd earlier in the neoadjuvant phase or reserve it for adjuvant use in patients who do not achieve a pathologic complete response. These studies highlight the potential for more personalized escalation strategies, though questions remain regarding optimal sequencing and long-term safety. In the metastatic setting, DESTINY-Breast09 reinforces the strong efficacy of T-DXd in previously untreated disease, prompting consideration of how best to integrate it with existing standards. For select HER2+/HR+ patients, a CLEOPATRA-based first-line regimen followed by a maintenance approach incorporating CDK4/6 inhibition, as explored in PATINA, may still offer a thoughtful alternative depending on clinical goals and patient characteristics.