Dr Cortés on Pooled Data for Trastuzumab Deruxtecan 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 primary outcomes and safety findings from a pooled analysis of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-positive metastatic breast cancer who have brain metastases. These data were derived from the phase 3 DESTINY-Breast01 (NCT03248492), DESTINY-Breast02 (NCT03523585), and DESTINY-Breast03 (NCT03529110) trials.

Findings from the pooled analysis were presented at the 2023 ESMO Congress and showed that T-DXd exhibited strong intracranial responses in patients with treated/stable and active brain metastases vs the comparator agents. In patients with stable brain metastases, T-DXd generated an intracranial objective response rate (IC-ORR) of 45.2%, along with a median intracranial duration of response (IC-DOR) of 12.3 months (range, 9.1-17.9), compared with 27.6% and 11.0 months (range, 5.6-16.0), respectively, in the comparator groups.

In patients with untreated or active brain metastases, T-DXd elicited an IC-ORR of 45.5% and a median IC-DOR of 17.5 months (range, 13.6-31.6) vs 12.0% and an undefined duration, respectively, in the comparator groups. Additionally, T-DXd yielded a numerically longer median central nervous system progression-free survival (CNS-PFS) in patients with both stable and active brain metastases and maintained an acceptable and manageable safety profile consistent with that seen in the overall patient population.

A total of 44 patients with untreated or active brain metastases received T-DXd, and 25 patients received the standard of care (SOC), Cortés begins. Conversely, 104 patients with stable or treated brain metastases received T-DXd, and 58 patients were treated with physician's choice of SOC, he explains. The IC-ORR and IC-DOR outcomes in these cohorts indicate T-DXd's superior activity vs SOC, Cortés emphasizes.

An exploratory CNS-PFS analysis conducted in the subgroup of patients with untreated active brain metastases demonstrated a median CNS-PFS of 4.0 months (95% CI, 2.7-5.7) with SOC vs18.5 months (95% CI, 13.6-23.3) with T-DXd, again emphasizing the activity of T-DXd in this patient group, Cortés continues. In terms of safety, adverse events (AEs) in patients with brain metastases were comparable with those observed in the overall population, with T-DXd–related serious treatment-emergent AEs reported in 13.0% of patients with brain metastases compared with 12.4% of patients in the overall population, respectively, he notes. Overall, T-DXd exhibited an acceptable and manageable safety profile in the overall population, with no significant differences in toxicity observed in patients with altered brain metastases, Cortés concludes.