T-DXd Preserves QOL, Brain Function in HER2+ Breast Cancer

SAN ANTONIO — More than half of patients with pretreated HER2-positive advanced or metastatic breast cancer who received the antibody-drug conjugate trastuzumab deruxtecan (T-DXd; Enhertu) had preservation of health-related quality of life (HRQOL) and neurological function at 1 year, even when the cancer had metastasized to brain, an analysis of data from the DESTINY-Breast12 trial shows.

For 504 patients with or without brain metastases at baseline, estimated deterioration-free rates at 12 months were greater than 50% for pain scores and for cognitive, emotional, physical, and social functioning scores, reported Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital in Munich, Germany, and colleagues.

“The findings for HRQOL and neurological function complement the overall clinical efficacy and safety profile of T-DXd in patients with HER2+ metastatic breast cancer, irrespective of the presence of stable or active brain metastases, and further support T-DXd as a valuable treatment option in this population,” they wrote in a scientific poster presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.

“We’re always worried about cognitive function in our patients with brain metastases, and we see that the cognitive function is well preserved in these patients with brain metastases compared to no baseline brain metastases,” commented Andrew J. Brenner, MD, PhD, from the Mays Cancer Center at UT Health San Antonio, who discussed the findings in a poster spotlight session. 

Open-label Trial

DESTINY-Breast12 is a phase 3b/4 open-label, multicenter international study evaluating the efficacy and safety of T-DXd in patients with breast tumors expressing high levels of HER2, with or without brain metastases, who had experienced disease progression on anti-HER2-based regimens and who had received no more than two prior lines of therapy in the metastatic setting (with the exception of tucatinib [Tukysa]).

In the analysis presented at SABCS, the investigators assessed HRQOL as the proportion of patients with clinically meaningful deterioration, defined as a decline from baseline of 4 more points for cognitive functioning, 8 or more points for Global Health Status, and 10 or more points for pain and physical functioning scores on the EORTC QLQ-C30 instrument.

In addition, they assessed declines in neurological function as a change from baseline scores to the worst score at any point during treatment on the Neurological Assessment in Neuro-Oncology scale and, for the cohort with baseline brain metastases, a score of 10 points or more (clinically meaningful) on brain-tumor specific outcomes in the MD Anderson Symptom Inventory.

As noted before, more than half of all patients in the cohorts with and without baseline brain metastases had no significant deterioration at 12 months of follow-up in domains of cognitive, emotional, physical and social functioning, and no significant deterioration in pain scores.

In addition, at the first time after the start of the trial that HRQOL and Neurological function were measured (weeks after the first doses were given), 55.1% of patients with baseline brain metastases and 72.9% without metastases had neurological stability. This stability was maintained throughout treatment. 

“Our patients are doing well on this regimen, and [it is] a regimen that seems to have activity,” Brenner summarized.

DESTINY-Breast12 is supported by AstraZeneca, co-developer of T-DXd with Daiichi Sankyo. Harbeck disclosed funding from both companies and others, and consulting fees from other pharmaceutical companies. Brenner disclosed consulting for Plus Therapeutics, speaking activities for Pfizer, grant/research support from Gilead and Plus, and ownership of NanoTx stock. 

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape Medical News.