Dr Cortés on Analyzing Outcomes With T-DXd in HER2+ Breast Cancer With Brain Metastases

Javier Cortés, MD, PhD, head, International Breast Cancer Center, clinical investigator, Breast Cancer Research Program, Vall d’Hebron Institute of Oncology, discusses the rationale for analyzing outcomes with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-positive metastatic breast cancer who have brain metastases. Findings from this pooled analysis were presented at the 2023 ESMO Congress based on data derived from the phase 3 DESTINY-Breast01 (NCT03248492), DESTINY-Breast02 (NCT03523585), and DESTINY-Breast03 (NCT03529110) trials.

The efficacy of T-DXd in HER2-positive metastatic breast cancer is tempered by the prevalence of brain metastases, which can significantly impact patient outcomes, Cortés begins. To shed light on the potential of T-DXd in patients with HER2-positive metastatic breast cancer with either stable or unstable brain metastases, investigators delved into an exploration of this agent’s efficacy and role within the framework of the DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03 trials, he states. However, the variability in inclusion and exclusion criteria across these trials adds complexity to the understanding of these pooled analysis outcomes, Cortés explains.

DESTINY-Breast01 exclusively enrolled heavily pretreated patients who had previously received ado-trastuzumab emtansine (T-DM1; Kadcyla). In this single-arm trial, all patients received T-DXd. In DESTINY-Breast02, patients previously treated with T-DM1 were randomized to receive either T-DXd or physician's choice of therapy, Cortés notes. Finally, DESTINY-Breast03 included patients with a treatment history involving a taxane and trastuzumab (Herceptin), and randomly assigned patients to receive either T-DXd or T-DM1, he explains.

The pooled analysis considered the nuances between these trial designs, Cortés continues. Initially, DESTINY-Breast02 and DESTINY-Breast03 permitted limited numbers of patients with previously untreated and asymptomatic brain metastases, as did DESTINY-Breast01. However, amendments to the DESTINY-Breast02 and DESTINY-Breast03 enrollment criteria restricted the inclusion of patients with unstable brain metastases, he emphasizes. Although most patients enrolled in these trials exhibited stable brain metastases, a minority presented with unstable brain metastases, adding depth to the exploration of T-DXd's impact across different metastatic scenarios, Cortés concludes.