T-DXd Versus Conventional Regimens for T-DM1–Pretreated, HER2-Positive Metastatic Breast Cancer

By: Julia Fiederlein Cipriano
Posted: Friday, February 3, 2023

According to Ian Krop, MD, PhD, of the Yale School of Medicine, New Haven, Connecticut, and colleagues, patients with HER2-positive unresectable and/or metastatic breast cancer who were previously treated with ado-trastuzumab emtansine (T-DM1) experienced superior progression-free and overall survival after treatment with fam-trastuzumab deruxtecan-nxki (T-DXd) compared with those who were treated with a conventional chemotherapy-based regimen. The primary results of the phase III DESTINY-Breast02 trial were presented during the 2022 San Antonio Breast Cancer Symposium (SABCS; Abstract GS2-01).

“[This trial] acts as a confirmatory study for the pivotal phase II DESTINY-Breast01 trial,” the investigators commented. “These data, together with earlier reported results from the DESTINY-Breast03 study of T-DXd versus T-DM1, solidify T-DXd as an optimal treatment option in patients with progressive HER2-positive metastatic breast cancer across broad settings.”

Patients were randomly assigned in a 2:1 ratio to receive T-DXd (n = 406) or the physician’s choice of either trastuzumab or lapatinib in combination with capecitabine (n = 202). The median durations of progression-free (17.8 vs. 6.9 months; hazard ratio [HR] = 0.36; P < .000001) and overall (39.2 vs. 26.5 months; HR = 0.66; P = .0021) survival were longer with T-DXd than with the chemotherapy-based regimens. The confirmed objective response and complete response rates were 69.7% and 14.0% with T-DXd and 29.2% and 5.0% with the chemotherapy-based regimens, respectively.

Treatment-emergent adverse events of grade 3 or higher were observed more frequently with T-DXd than with the chemotherapy-based regimens (52.7% vs. 44.1%). Adjudicated drug-related interstitial lung disease was reported in 10.4% of patients treated with T-DXd and in 0.5% of those who received a chemotherapy-based regimen. In the population treated with T-DXd, 88.1% of the cases of interstitial lung disease were grade 1 or 2; grade 5 interstitial lung disease occurred in 0.5% of patients.

Disclosure: For full disclosures of the study authors, visit sabcs.org.

2022 San Antonio Breast Cancer Symposium