A patient's time to progression on first-line CDK4/6 inhibitor therapy acts as an informal biomarker. A shorter duration, such as 14 months, is viewed by experts as "not so great" and indicates a degree of underlying endocrine resistance that influences subsequent treatment strategies.
A subtle finding in the DESTINY-Breast11 trial, where TDXD alone underperformed TDXD followed by THP, suggests that taxane-based chemotherapy might remain effective even after a patient's HER2-positive cancer becomes resistant to the antibody-drug conjugate TDXD.
While oncologists focus on the low 4% rate of Interstitial Lung Disease (ILD) from neoadjuvant TDXD, surgeons worry this complication could prevent patients from reaching potentially curative surgery, drawing parallels to issues seen with neoadjuvant immunotherapy.
Due to cumulative toxicity concerns with TDXD, particularly ILD, clinicians express more comfort with the shorter 4-cycle neoadjuvant course from DESTINY-Breast11 than the prolonged 14-cycle adjuvant therapy in DESTINY-Breast05, favoring front-loading the treatment.
Clinicians lack evidence to guide treatment for triple-negative breast cancer that relapses shortly after neoadjuvant chemo-immunotherapy. Pivotal trials for new ADCs like Dato-DXD included very few patients with prior immunotherapy, creating a significant and common evidence gap in clinical practice.
Positive data from both DESTINY-Breast09 (TDXD-based) and PATINA (CDK4/6i maintenance) create a new dilemma. With similar PFS outcomes, the first-line choice for metastatic HER2+/HR+ patients now hinges on toxicity profiles and patient preference rather than a single efficacy winner.