Pooled analysis of the DESTINY Breast 01, -02, and -03 trials focusing on brain metastases

During ESMO 2023 Prof Hurvitz, affiliated with the Fred Hutch Cancer Center in Seattle, discussed with Dr Eline Naert from UZ Ghent the pooled analysis of the DESTINY Breast 01, -02,  and -03 trials, focusing on a specific subgroup: patients with brain metastases. The analysis revealed a remarkable intracranial objective response rate of 45% among patients treated with T-DXd (trastuzumab deruxtecan), indicating a significant therapeutic impact. This outcome was observed in patients with both stable, previously treated brain metastases and those with untreated active brain metastases.

The conversation also touched upon the shifting landscape regarding the use of tucatinib versus T-DXd in clinical practice. It was highlighted that while these data were compelling, they may not directly replace tucatinib, as the analysis was exploratory and not derived from prospective randomized trials. Tucatinib’s effectiveness was demonstrated in the HER2-CLIMB study, which included a substantial number of patients with active brain metastases, setting it apart from the T-DXd data.

Furthermore, there was a consideration of the patient population’s diversity, notably the predominance of Asian patients in the DESTINY trials compared to a more Caucasian patient population in Belgium. Prof Hurvitz emphasised that there weren’t substantial differences in outcomes based on the country of origin. Any potential variations appeared to be related to toxicity profiles rather than efficacy, making the findings applicable across diverse patient groups.

Lastly, a scenario involving a patient receiving taxane in combination with HER2-targeted therapies who developed intracranial progressive disease alongside an extracranial complete response was discussed. Prof Hurwitz recommended considering options such as tucatinib, particularly if the patient was eligible for the HER2-CLIMB trial, which supported its use in this context. However, for T-DXd, the analysis was not designed for patients with intracranial progression as the sole site of disease. Future studies, like TUXEDO and Breast07, are expected to provide more comprehensive insights for making treatment decisions in similar cases. 

In conclusion, Prof Hurvitz’s insights shed light on the evolving landscape of HER2-positive breast cancer treatments, especially in the context of brain metastases, and emphasized the need for personalized patient care based on the available evidence.

Reference:

Sara A. Hurvitz  – A Pooled Analysis of Trastuzumab Deruxtecan (T-DXd) in Patients (pts) With HER2-Positive (HER2+) Metastatic Breast Cancer (mBC) With Brain Metastases (BMs) from DESTINY-Breast (DB) -01, -02, and -03 – ESMO 2023 – 377O