Dr Yuan on the DEMETHER Trial of Induction T-DXd Plus HP Maintenance in HER2+ Breast Cancer

"I believe [the DEMETHER] approach will be perhaps more welcomed in clinical practice [than the DESTINY-Breast09 approach]. Not every trial is comparable, but we're looking forward to the DEMETHER data to confirm our approach of induction [T-DXd] followed by maintenance [trastuzumab plus pertuzumab]."

Yuan Yuan, MD, PhD, the director of Breast Medical Oncology Medicine and the medical director of the Breast Oncology Disease Research Group at Cedars-Sinai Medical Center, as well as a health sciences clinical professor at the University of California, Los Angeles, discussed ongoing efforts to refine the optimal sequencing of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for patients with HER2-positive unresectable, locally recurrent, or metastatic breast cancer.

Yuan began by highlighting the phase 2 DEMETHER study (NCT06172127), which is evaluating a sequential strategy that may be more readily applied in routine practice. In DEMETHER, patients received an induction phase consisting of 6 cycles of T-DXd, followed by a maintenance phase with fixed-dose trastuzumab (Herceptin) and pertuzumab (Perjeta). Yuan noted that this design aims to balance efficacy with long-term tolerability by front-loading a high-activity regimen and then transitioning to maintenance therapy to sustain control of metastatic disease.

She contrasted this approach with the phase 3 DESTINY-Breast09 regimen, which combined T-DXd with pertuzumab in the upfront setting.

Although not directly comparable studies, DESTINY-Breast09 introduced the concept of intensified first-line therapy for HER2-positive metastatic disease, whereas DEMETHER will help determine whether sequential induction and maintenance can achieve similar benefit while potentially minimizing cumulative toxicity from continuous T-DXd exposure.

Yuan concluded that findings from DEMETHER will be important in validating induction-maintenance treatment paradigms and may help solidify a practical and scalable approach for patients with HER2-positive metastatic breast cancer.